| 1. |
- Behboudi, Afrouz, 1967, et al.
(författare)
-
Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion.
- 2005
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 43:2, s. 202-5
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that the t(11;19)(q21;p13) translocation in mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the N-terminal CREB-binding domain of the cAMP coactivator TORC1 (a.k.a. MECT1 and WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type, clear cell hidradenoma of the skin, also expresses this gene fusion. RT-PCR analysis of a clear cell hidradenoma with a t(11;19)(q21;p13) translocation revealed expression of a TORC1-MAML2 fusion transcript consisting of exon 1 of TORC1 fused to exons 2-5 of MAML2. Because the fusion was only detected in a single case, the frequency of this aberration in clear cell hidradenomas remains unknown. These results demonstrate that the t(11;19) in mucoepidermoid carcinoma, Warthin's tumor, and clear cell hidradenoma targets the same genes and results in identical gene fusions, indicating that at least subgroups of these glandular tumors evolve through activation of the same molecular pathways.
|
|
| 2. |
- Enlund, Fredrik, 1968, et al.
(författare)
-
Molecular analyses of the candidate tumor suppressor gene, PLAGL1, in benign and malignant salivary gland tumors
- 2004
-
Ingår i: EUROPEAN JOURNAL OF ORAL SCIENCES. - : Wiley. - 0909-8836 .- 1600-0722. ; 112:6, s. 545-547
-
Tidskriftsartikel (refereegranskat)abstract
- Deletions affecting the long arm of chromosome 6 are a characteristic feature of all major subtypes of malignant salivary gland tumors. Moreover, a subgroup of adenoid cystic carcinomas have t(6;9)(q23-25;p21-24) translocations with breakpoints located within the commonly deleted region. Here we have examined the possible involvement of the candidate tumor suppressor gene, PLAGL1, in these deletions and translocations. Northern blot and fluorescence in situ hybridization (FISH) analyses of a series of 27 salivary gland tumors revealed no significant changes in the gene expression or rearrangements of PLAGL1. FISH analysis also demonstrated that the 6q translocation breakpoint in adenoid cystic carcinomas with t(6;9) is proximal to the PLAGL1 locus. Collectively, these results indicate that PLAGL1 is not likely to be the major target gene of the 6q rearrangements in salivary gland tumors.
|
|
| 3. |
- Enlund, Mats, et al.
(författare)
-
Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane
- 2023
-
Ingår i: EClinicalMedicine. - : Elsevier. - 2589-5370. ; 60
-
Tidskriftsartikel (refereegranskat)abstract
- Background Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and perprotocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.
|
|
| 4. |
- Enlund, Mats, et al.
(författare)
-
Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients
- 2020
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 64:8, s. 1048-1054
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival.Methods: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis.Results: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95).Conclusions: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.
|
|
| 5. |
- Persson, Fredrik, 1973, et al.
(författare)
-
High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes
- 2008
-
Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 27:21, s. 3072-3080
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously identified a subgroup of pleomorphic salivary gland adenomas with ring chromosomes of uncertain derivation. Here, we have used spectral karyotyping (SKY), fluorescence in situ hybridization (FISH) and high-resolution oligonucleotide array-CGH to determine the origin and content of these rings and to identify genes disrupted as a result of ring formation. Of 16 tumors with rings, 11 were derived from chromosome 8, 3 from chromosome 5 and 1 each from chromosomes 1, 6 and 9. Array-CGH revealed that 10/11 r(8) consisted of amplification of a 19 Mb pericentromeric segment with recurrent breakpoints in FGFR1 in 8p12 and in PLAG1 in 8q12.1. Molecular analyses revealed that ring formation consistently generated novel FGFR1-PLAG1 gene fusions in which the 5'-part of FGFR1 is linked to the coding sequence of PLAG1. An alternative mechanism of PLAG1 activation was found in tumors with copy number gain of an intact PLAG1 gene. Rings derived from chromosomes 1, 5, 6 or 9 did not result in gene fusions, but rather resulted in losses indicative of the involvement of putative tumor suppressor genes on 8p, 5p, 5q and/or 6q. Our findings also reveal a novel mechanism by which FGFR1 contributes to oncogenesis and further illustrate the versatility of the FGFR1 and PLAG1 genes in tumorigenesis.
|
|
| 6. |
- Winnes, Marta, 1979, et al.
(författare)
-
Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas
- 2007
-
Ingår i: Genes Chromosomes Cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 46:6, s. 559-563
-
Tidskriftsartikel (refereegranskat)abstract
- Fusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1-MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1-MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1-MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion-positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion-negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1-MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.
|
|
| 7. |
- Andersson, Carola, et al.
(författare)
-
Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2 : a paediatric case report and review of the literature
- 2014
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:4, s. 1608-1612
-
Forskningsöversikt (refereegranskat)abstract
- Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas: The relevant literature is reviewed and further discussed in relation to our findings.
|
|
| 8. |
- Behboudi, Afrouz, 1967, et al.
(författare)
-
Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
- 2006
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 45:5, s. 470-81
-
Tidskriftsartikel (refereegranskat)abstract
- Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1-MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs.
|
|
| 9. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
-
Cytogenetic analysis of 477 psoriatics revealed an increased frequency of aberrations involving chromosome region 11q
- 1999
-
Ingår i: Eur J Hum Genet. ; 7:3, s. 339-44
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is an inflammatory skin disorder affecting approximately 3% of the population. Genetic studies published so far have shown a complex genetic inheritance with heterogeneity and a putative major susceptibility locus in the HLA region on chromosome 6. We have collected a large amount of material consisting mostly of small nuclear families in order to perform a genome-wide scan for psoriasis-associated genes. In order to focus the scan properly on possible candidate regions, we performed a cytogenetic analysis of 477 unrelated psoriatics. We divided our findings into sporadic, affecting a minor fraction of the cells, and constitutional, i.e. they were present in all cells examined. We found three cases of balanced translocation, all of which involved chromosome 11q. Two of these had a breakpoint in q12-13, whilst one involved the telomeric part of chromosome 11q. In order to characterise further the breakpoint on 11q12-13, we used bacterial artificial chromosomes (BACs) analysed by fluorescent in situ hybridisation (FISH). We were able to show that the persons had a close, but not identical breakpoints; they were separated by at least 5 cM. The major atopy locus is located in this region, as well as a locus for insulin-dependent diabetes mellitus, both being conditions with a pathogenetic mechanism involving antigen presentation.
|
|
| 10. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
-
Evidence that HLA-Cw6 determines early onset of psoriasis, obtained using sequence-specific primers (PCR-SSP)
- 1997
-
Ingår i: Acta Derm Venereol. ; 77:4, s. 273-6
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis vulgaris has previously been shown to associate with certain HLA alleles. HLA-Cw6 is considered to be the primary association, based on calculations of relative risk after serological typing. This association is reportedly more pronounced in early- than in late-onset psoriasis. We performed a PCR-based typing with sequence-specific primers, which has been shown to give a more complete result than serology. Two hundred and one unrelated patients with psoriasis, with a mean age of 40 years, and 77 healthy controls were typed. Two thirds (67%) of the patients were positive for one or two copies of the allele, while the corresponding figure for the control group was 12%. A significant peak for age at onset of 21 or younger was seen for the Cw6 carriers. For patients older than 21 at onset, the frequency of Cw6 was significantly lower; e.g. for patients with an age at onset between 30 and 35 the frequency was comparable to the level of the control group. The high frequency of Cw6 among patients with an age at onset of 21 or younger is in agreement with data of other groups. In comparison with this age-at-onset group the frequency of Cw6 is sharply reduced among patients with an age at onset of 22 years or older, which contrasts with earlier studies. This may reflect differences between population groups but may also be due to the higher sensitivity of the PCR-based HLA-Cw6 typing method. In view of these findings, we suggest that psoriasis is a genetically determined disease, in which the additional presence of HLA-Cw6 is associated with the characteristic of early onset.
|
|
| 11. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
-
S gene (Corneodesmosin) diversity and its relationship to psoriasis; high content of cSNP in the HLA-linked S gene
- 2000
-
Ingår i: J Invest Dermatol. - 0022-202X .- 0022-202X. ; 114:6, s. 1158-63
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a heterogeneous disease in which several reports suggest the presence of a susceptibility gene in or in the proximity of the human leukocyte antigen complex in chromosome 6p. There is an association between HLA-Cw6 and young onset of the disease. The S gene (corneodesmosin), located 160 kb telomeric of HLA-C, is a strong candidate for psoriasis due to its reportedly exclusive expression in differentiating keratinocytes. We have studied this gene in a large Swedish psoriasis population and we report a strikingly high degree of polymorphism in the coding parts of the gene, 1 every 100 base pairs. We used a stratified approach to compare the polymorphic variants in patients and controls. A single nucleotide polymorphism in the coding region leading to an amino acid exchange (Ser-->Phe) that differed significantly between patients and controls was identified (position 619). Owing to a high allele frequency in a larger control group, however, and an insignificant influence of the variant on the age at onset distribution curve based on a large psoriasis population, we could not confirm that this coding single nucleotide polymorphism was involved in disease etiology. We also examined the single nucleotide polymorphism in position 1243, recently proposed to have an influence on the pathogenesis of the disease. This polymorphism showed less association to the disease as compared with the single nucleotide polymorphism at positions 619 and 722. Such a high degree of variation present also in an HLA gene which is not involved in immune response indicates the difficulty involved in assessing the role of a specific allele in the pathogenesis of a complex disease in this region. A strong association effect due to linkage disequilibrium in an extended region in the HLA complex is also a complicating factor.
|
|
| 12. |
|
|
| 13. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
-
Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients.
- 2000
-
Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 292:11, s. 525-30
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis vulgaris is strongly associated with certain human leukocyte antigens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was utilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haplotype information were sequenced. The results confirmed the identity of the Cw6 allele in affected individuals with the consensus sequence for Cw*0602. We screened the set of families for psoriasis patients homozygous for Cw6 and found 11 individuals with a mean age at onset of 16.1 years. The corresponding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-negatives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t167/nt45). This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested candidate gene in the region. The maximum nonparametric linkage (NPL) value was also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the highest degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a polygenic theory.
|
|
| 14. |
- Enlund, Fredrik, 1968, et al.
(författare)
-
Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
- 2004
-
Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 292:1, s. 21-8
-
Tidskriftsartikel (refereegranskat)abstract
- Chromosome translocations in neoplasia commonly result in fusion genes that may encode either novel fusion proteins or normal, but ectopically expressed proteins. Here we report the cloning of a novel fusion gene in a common type of salivary and bronchial gland tumor, mucoepidermoid carcinomas (MEC), as well as in benign Warthin's tumors (WATs). The fusion, which results from a t(11;19)(q21-22;p13) translocation, creates a chimeric gene in which exon 1 of a novel gene of unknown function, designated WAMTP1, is linked to exons 2-5 of the recently identified Mastermind-like Notch coactivator MAML2. In the fusion protein, the N-terminal basic domain of MAML2, which is required for binding to intracellular Notch (Notch ICD), is replaced by an unrelated N-terminal sequence from WAMTP1. Mutation analysis of the N-terminus of WAMTP1-MAML2 identified two regions of importance for nuclear localization (amino acids 11-20) and for colocalization with MAML2 and Notch1 ICD in nuclear granules (amino acids 21-42). Analyses of the Notch target genes HES5 and MASH1 in MEC tumors with and without the WAMTP1-MAML2 fusion revealed upregulation of HES5 and downregulation of MASH1 in fusion positive MECs compared to normal salivary gland tissue and MECs lacking the fusion. These findings suggest that altered Notch signaling plays an important role in the genesis of benign and malignant neoplasms of salivary and bronchial gland origin.
|
|
| 15. |
- Enlund, Fredrik, 1968, et al.
(författare)
-
Analysis of three suggested psoriasis susceptibility loci in a large Swedish set of families: confirmation of linkage to chromosome 6p (HLA region), and to 17q, but not to 4q
- 1999
-
Ingår i: Hum Hered. ; 49:1, s. 2-8
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is known to be a heterogeneous disease with so far three reported major psoriasis susceptibility loci on chromosome 4q, 6p and 17q. In this study we investigated three reported gene locations by nonparametric and parametric linkage analysis in a large family set consisting of 104 families (153 sib pairs) from Sweden. We could confirm linkage to chromosome 6p. A maximum heterogeneous lod score of 2.78 was reached at locus D6S276 (alpha = 0.60). Allelic association studies within the HLA region indicated linkage disequilibrium at locus TNFbeta with a significant p value of 0.0009. Furthermore, we obtained weak evidence of linkage to the locus on chromosome 17q while no evidence of linkage could be found to the chromosome 4q region.
|
|
| 16. |
- Enlund, Fredrik, 1968
(författare)
-
Genetic susceptibility to psoriasis in Sweden
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A common skin disease affecting about 2-3% of the population, psoriasis has an inheritance pattern that is unclear, but most probably many genes are involved in its pathogenesis. Other studies have suggested many susceptibility regions in the genome, but as yet independent studies have replicated only some of these regions located on chromosome 1q, 6p and 17q.In searching for psoriasis candidate regions, we analysed a large Swedish psoriasis material that comprised 104 families; in each of which both parents were healthy but two or more siblings were affected with psoriasis. We amplified polymorphic microsatellite markers with PCR technology; the fragments were separated on an ABI 377 sequencer. Having made a statistical linkage analysis that defined regions of interest for further investigation, we could show strong evidence that there is a psoriasis susceptibility region at chromosome 6p (HLA region) and also narrow the region by showing evidence for allelic association to one of the markers (TNFb). We made a stratified genome scan of families in which both psoriasis and joint complaints occurred. The HLA region on chromosome 6p showed stronger linkage in the group without joint complaints. The region on chromosome 17q noted above showed strong linkage in the joint-complaint cohort. Other suggested susceptibility regions on chromosome 1q and 4q showed no linkage in our material. On chromosome 3q21, we also identified a novel region that was linked to joint-complaint families. This chromosomal region was confirmed through stratification of families from south-western Sweden. An independent material (148 families) also confirmed the finding. In an allelic association test, we obtained a significant deviation at markers D3S1269 and D3S1551 that suggests a geographically isolated mutation is present among individuals having joint complaints. This psoriasis susceptibility locus on chromosome 3q21 has been denoted PSORS5. We investigated two candidate genes involved in the proliferation of T-cells, CD80 and CD86, that are located in the chromosome 3q21 region. In the coding or promotor sequence, we found no evidence for mutation in either gene, which suggests neither is responsible for any occurrence of psoriasis.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Enlund, Fredrik, 1968, et al.
(författare)
-
Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden
- 1999
-
Ingår i: Eur J Hum Genet. ; 7:7, s. 783-90
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed a pair-wise linkage study in the search for psoriasis susceptibility regions. A preliminary scan was performed on 20 families. In this set we obtained indications of linkage on chromosome 3q21. This region was further investigated using material from a total of 104 families (set 1B) resulting in a non-parametric linkage (NPL) of 1.77. The material was stratified in families whose parental origin is in southwest Sweden (set 1C). A maximum NPL value of 2.77 was obtained in this group. A transmission disequilibrium test (TDT) was performed on the stratified material (set 1C) and a significant P value of 0.005 was obtained, at marker D3S1269. The locus was confirmed with TDT in replicate material consisting of 148 families in which a single member was affected (P value 0.0007) at marker D3S1551. Thus, we have observed a significant P value using TDT in the vicinity of markers D3S1269/D3S1551, suggesting a novel psoriasis susceptibility region.
|
|
| 20. |
- Enlund, Johannes, et al.
(författare)
-
Anisotropic dry etching of boron doped single crystal CVD diamond
- 2005
-
Ingår i: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 43:9, s. 1839-1842
-
Tidskriftsartikel (refereegranskat)abstract
- Semiconducting boron doped single-crystal CVD diamond has been patterned using aluminum masks and an inductively coupled plasma (ICP) etch system. For comparison insulating HPHT diamond samples were also patterned using the same process. Diamond etch rates above 200 nm/min were obtained with an O2/Ar discharge for a gas pressure of 2.5 mTorr using 600 W RF power. We have accomplished the fabrication of structures with a minimum feature size of 1 μm with vertical sidewalls in both CVD and HPHT diamond. The ICP etching produced smooth surfaces with a typical root-mean-square surface roughness of 3 nm. The dependence of etch rate on bias voltage was somewhat different for the two types of diamond. However, for all samples both the etch rate and anisotropy were found to improve with increasing bias voltage.
|
|
| 21. |
- Enlund, Jakob, 84, et al.
(författare)
-
Individual Carbon Footprint Reduction: Evidence from Pro-environmental Users of a Carbon Calculator
- 2022
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We provide the first estimates of how pro-environmental consumers reduce their total carbon footprint using a carbon calculator that covers all financial transactions. We use data from users of a carbon calculator that includes weekly estimates of users’ consumptionbased carbon-equivalent emissions based on detailed financial statements, official registers, and self-reported life-style factors. The calculator is designed to induce behavioral change and gives users detailed information about their footprint, and includes social comparisons, and goal-setting options. By using a robust difference-in-differences analysis with staggered adoption of the calculator, we estimate that users decrease their carbon footprint by around 10 percent in the first few weeks, but over the next few weeks, the reduction fades. Further analysis suggests that the carbon footprint reduction is driven by a combination of a shift from high- to low-emitting consumption categories and a temporary decrease in overall spending, and not by changes in any specific consumption category.
|
|
| 22. |
- Enlund, Jakob, et al.
(författare)
-
Individual Carbon Footprint Reduction: Evidence from Pro-environmental Users of a Carbon Calculator
- 2023
-
Ingår i: Environmental & Resource Economics. - : Springer. - 0924-6460 .- 1573-1502. ; 86, s. 433-467
-
Tidskriftsartikel (refereegranskat)abstract
- We provide the first estimates of how pro-environmental consumers reduce their total carbon footprint using a carbon calculator that covers all financial transactions. We use data from Swedish users of a carbon calculator that includes weekly estimates of users' consumption-based carbon-equivalent emissions based on detailed financial statements, official registers, and self-reported lifestyle factors. The calculator is designed to induce behavioral change and gives users detailed information about their footprint. By using a robust difference-in-differences analysis with staggered adoption of the calculator, we estimate that users decrease their carbon footprint by around 10% in the first few weeks, but over the next few weeks, the reduction fades. Further analysis suggests that the carbon footprint reduction is driven by a combination of a shift from high- to low-emitting consumption categories and a temporary decrease in overall spending, and not by changes in any specific consumption category.
|
|
| 23. |
- Gustafsson Asting, Annika, et al.
(författare)
-
Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer.
- 2014
-
Ingår i: Journal of Cancer Therapy. - : Scientific Research Publishing, Inc.. - 2151-1934 .- 2151-1942. ; 5:14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer; these DNA alterations may have been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.
|
|
| 24. |
- Hallqvist, Andreas, 1973, et al.
(författare)
-
Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with high-dose radiotherapy.
- 2012
-
Ingår i: Lung Cancer International. - : Hindawi Limited. - 2090-3200 .- 2090-3197. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.
|
|
| 25. |
- Hewett, D., et al.
(författare)
-
Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map
- 2002
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 0888-7543. ; 79:3, s. 305-14
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.
|
|
| 26. |
- Holmberg, Lars, et al.
(författare)
-
Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer
- 2022
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9 September
-
Tidskriftsartikel (refereegranskat)abstract
- Background Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer. Aim We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample. Methods We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years. Results Overall survival and survival from causes other than bladder cancer estimated with Kaplan- Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up. Conclusion The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding. © 2022 Holmberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|
|
| 27. |
- Inerot, Annica, 1949, et al.
(författare)
-
Collecting a set of psoriasis family material through a patient organisation; clinical characterisation and presence of additional disorders.
- 2005
-
Ingår i: BMC Dermatology. - : Springer Science and Business Media LLC. - 1471-5945. ; 5:10
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to describe the clinical characteristics of a population of psoriatics sampled from a patient organisation and not from hospitals or out-patient clinics. Furthermore, we wanted to compare siblings with and without psoriasis regarding the occurrence of other diseases.At the end of 1991, we initiated a project which aimed to study genetic factors leading to psoriasis. Firstly, we sent questionnaires to all the members of the Swedish Psoriasis Association. We then examined 1,217 individuals (570 with psoriasis) from 310 families, in their homes in the southern part of Sweden. All the available family members were examined clinically and asked about the course of the skin disease and the occurrence of other diseases. The eight hundred members of the proband generation were divided into two groups, with or without psoriasis, and their clinical features were compared.Most individuals in this study population had a mild form of psoriasis. The siblings with psoriasis had joint complaints significantly more frequently than their siblings without the skin disease and those with joint complaints had more widespread skin disease. Among the other studied concomitant diseases (iritis, heart or hypertension disease, endocrine disease, inflammatory bowel disease and neurological disease), we were not able to find any difference. Seventy-seven of 570 persons were found to be in remission (13.5%). Females had a mean onset 2.5 years earlier than males. We were not able to find any correlation between the extent of the skin disease and age at onset. Twice as many persons with joint complaints were found among those with psoriasis than among those without, 28% versus 13%. Almost half (48%) the psoriatics who also had joint complaints had psoriasis lesions on their nails. Endocrine disorders were found in 9% of those without any allele for Cw6, but only in 1% of those who had Cw6. In fact, none of 183 Cw6 carriers had diabetes, as compared to the population prevalence of 3-5% in Sweden.With the exception of joint complaints, persons with psoriasis, collected from a patient organisation, did not have an increased frequency of (studied) co-existing diseases.
|
|
| 28. |
- Isaksson, Johan, et al.
(författare)
-
KRAS G12C mutant non-small cell lung cancer linked to female sex and high risk of CNS metastasis : Population-based demographics and survival data from the National Swedish Lung Cancer Registry
- 2023
-
Ingår i: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 24:6, s. 507-518
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundReal-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved.MethodWe identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349).ResultsThe prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt.ConclusionThe KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.
|
|
| 29. |
- Lagerstedt, Kristina, 1976, et al.
(författare)
-
Genes with relevance for early to late progression of colon carcinoma based on combined genomic and transcriptomic information from the same patients.
- 2010
-
Ingår i: Cancer informatics. - 1176-9351. ; 9, s. 79-91
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. METHODS: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. RESULTS: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A-D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. CONCLUSIONS: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.
|
|
| 30. |
- Samuelsson, Lena, 1962, et al.
(författare)
-
A genome-wide search for genes predisposing to familial psoriasis by using a stratification approach
- 1999
-
Ingår i: Hum Genet. - 0340-6717 .- 0340-6717. ; 105:6, s. 523-9
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed a genome scan, using markers spaced by 10 cM, in the search for psoriasis-susceptibility loci. The family material of 134 affected sibling pairs was ascertained on the basis of a population genetic study in which 65% of the probands had two healthy parents. Genotyping results were analyzed for non-random excessive allele-sharing between sib pairs by using GENEHUNTER ver 1.1. A stratification approach was applied to increase the homogeneity of the material by means of an operational definition of joint complaints among affected individuals. Significant linkage to the human leukocyte antigen region on chromosome 6p in a cohort including 42 families without joint complaints (nonparametric linkage score of 2.83, P=0.002) strongly supported the validity of this operational definition as it replicated results from an earlier linkage report with similar stratification criteria. New candidate regions on chromosomes 3 and 15 were identified. The highest non-parametric linkage values in this study, 2.96 (P=0.0017) and 2.89 (P=0.0020), were reached on chromosome 15 in a subgroup with joint complaints and on chromosome 3 in a subgroup without joint complaints. In addition, confirmation of previously reported loci was established on chromosomes 4q, 6p, and 17q. This study indicates that distinct disease loci might be involved in psoriasis etiology for various phenotypes.
|
|
| 31. |
- Silfverberg, Thomas, et al.
(författare)
-
Late onset hyperornithinemia-hyperammonemia-homocitrullinuria syndrome : how web searching by the family solved unexplained unconsciousness: a case report
- 2018
-
Ingår i: Journal of Medical Case Reports. - : Dove Medical Press. - 1752-1947. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a rare inherited urea cycle disorder, can remain undiagnosed for decades and suddenly turn into an acute life-threatening state. Adult presentation of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome has rarely been described, but is potentially underdiagnosed in the emergency room. In the case of acute hyperammonemia, prompt diagnosis is essential to minimize the risk of brain damage and death.Case presentation: We present the diagnostics, clinical course, and treatment of a 48-year-old Caucasian man presenting with unexplained unconsciousness in the emergency room. A web search by a family member led to the suspicion of urea cycle disorder. Subsequent analysis of plasma ammonia and amino acids in plasma and urine demonstrated a pattern typical for hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. The diagnosis was confirmed by genetic analysis which revealed two heterozygous mutations in the SLC25A15 gene. The cause of the hyperammonemia crisis was acute upper gastrointestinal hemorrhage, leading to protein overload and subsequent cerebral edema. Continuous renal replacement therapy, scavenger treatment, and tightly controlled nutrition were useful in preventing hyperammonemia and recurrence of cerebral edema.Conclusions: The case emphasizes the importance of taking rare metabolic genetic disorders into consideration in patients with prolonged unexplained unconsciousness.
|
|
| 32. |
- Stenman, Lisa, et al.
(författare)
-
Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case.
- 2016
-
Ingår i: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 5:5, s. 593-595
-
Tidskriftsartikel (refereegranskat)abstract
- Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph node. Histopathological analysis of both lesions revealed infiltration by medium-sized neoplastic lymphoid cells with a high nuclear-cytoplasmic ratio and a high mitotic index. Immunostaining revealed positivity for CD2, CD3, CD99, Tia-1, and GranzymB, and variable positivity for CD4. There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms.
|
|
| 33. |
|
|
| 34. |
- Svensson, Maria, 1980-
(författare)
-
Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease.The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa.The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts.The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.
|
|
| 35. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
-
Age at onset and different types of psoriasis
- 1995
-
Ingår i: Br J Dermatol. ; 133:5, s. 768-73
-
Tidskriftsartikel (refereegranskat)abstract
- The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 179 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (P < 0.001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0.30 and 0.45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0.25, the next earliest, 0.18, and the latest, 0.14.
|
|
| 36. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
-
Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands
- 1997
-
Ingår i: Br J Dermatol. ; 137:6, s. 939-42
-
Tidskriftsartikel (refereegranskat)abstract
- The risk of getting psoriasis dependent on the occurrence of psoriasis in the family has been determined empirically. Altogether 3717 families with one or both parents who had psoriasis have been analysed with regard to the number of children with or without psoriasis. The lifetime risk of getting psoriasis if no parent, one parent or both parents have psoriasis is 0.04, 0.28 and 0.65, respectively. If there is already one affected child in the family, the corresponding risks are 0.24, 0.51 and 0.83, respectively. The risk of getting psoriasis before the age of 32 years is dependent on the age-of-onset of psoriasis in one affected parent.
|
|
| 37. |
- Thulin, Anna, 1978, et al.
(författare)
-
Clinical outcome of patients with brain metastases from breast cancer - A population based study over 21 years.
- 2020
-
Ingår i: Breast. - : Elsevier BV. - 1532-3080. ; 50, s. 113-124
-
Tidskriftsartikel (refereegranskat)abstract
- Brain metastases (BM) are a feared progression of breast cancer (BC) with impact on quality of life and survival. Despite improved treatments, it is believed patients suffering from BM are increasing.To study potential changes in the number of BM, the possible links between BC subgroup and extent of BM with prognosis. To investigate the interval between primary BC/extra cranial recurrence, and diagnosis of BM in the years 1994-2014.Clinical data from 191 patients with BM diagnosed 1994-2014, was retrieved from charts. Primary tumours where re-evaluated histologically.There was an increase of BM in 5 years cohorts (1994-99 (n=9); 2000-04 (n=36); 2005-09 (n=60); 2010-14 (n=86)). We found no difference in the time interval from primary BC to BM but an insignificant increase in time from extra cranial relapse to development of BM in the time periods 1994-2004 and 2005-2014 of 15.5 and 25.0 months (p=0.0612). Survival after BM was 7 months (95% CI 6-10) with a statistically significant difference between HER2 positive and TNBC with an inferior outcome for the latter (p=0.018) whilst no differences were present when Luminal BC were compared with HER2 positive BC (p=0.073).We show an increase of BM over time whilst the time span from primary BC to BM is unchanged supports earlier findings that adjuvant treatments have little preventive function. Time from extra cranial recurrence to BM was prolonged with one year. Patients with TNBC or more advance extent of BM had the shortest survival with BM.
|
|
| 38. |
- Thulin, Anna, 1978, et al.
(författare)
-
Discordance of PIK3CA and TP53 mutations between breast cancer brain metastases and matched primary tumors.
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- There is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal A-/B-like, HER2+and TNBC) of BCBM, and to determine survival according to specific mutations. We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.
|
|
| 39. |
|
|
