SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Borg Åke) srt2:(2015-2019)"

Sökning: WFRF:(Borg Åke) > (2015-2019)

  • Resultat 21-30 av 70
  • Föregående 12[3]4567Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
21.
  • Ehinger, Anna, et al. (författare)
  • Myoepithelium assessment with p63 immunostaining in formalinfixed paraffin-embedded breast cancer tissue pre-treated with RNA-later
  • 2017
  • Ingår i: Virchows Archiv. - Springer. - 1432-2307. ; 471:Supplement 1, s. 299-299
  • Konferensbidrag (refereegranskat)abstract
    • Objective: To assessmyoepithelium with p63 in fresh breast cancer (BC)tissue samples collected in RNA later for further analysis with NextGeneration Sequencing (NGS) technique. For a better understanding ofthe NGS bulk-analysis, a central part of the sample in RNA-later isformalin-fixed paraffin-embedded to score relative cellularity in % onhematoxylin-eosin (HE) staining (% of invasive cancer, cancer in situ,benign epithelium, lymphocytes and fat). Our aim is hence to test p63immunohistochemistry (IHC) to highlight myoepithelium and to facilitatethe evaluation of the relative cellularity on BC-tissue pre-treated withRNA-later.Method: Two-hundred and twenty-four selected samples of fresh BCtissue collected in RNA-later. A 10 mg central piece from each samplewas FFPE and assembled in a tissue-microarray (TMA) and sectioned toHE and p63 IHC.Results: All samples (n = 224) had internal control for myoepitheliumsurrounding in situ cancer or benign epithelium. p63 showed positivenuclear staining in myoepithelial cells in 92 % (206/224) of samplesand false negative p63 staining in 8 % (18/224).Conclusion: p63 IHC is assessable in samples of FFPE BC-tissue pretreatedwith RNA-later.
22.
  • Ellberg, Carolina, et al. (författare)
  • Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort.
  • 2015
  • Ingår i: Genes, Chromosomes and Cancer. - John Wiley & Sons. - 1045-2257. ; 54:1, s. 39-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
  •  
23.
  • Fang, Jun, et al. (författare)
  • Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.
  • 2017
  • Ingår i: Nature Communications. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
24.
  • Galeev, Roman, et al. (författare)
  • Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs
  • 2016
  • Ingår i: Cell Reports. - Cell Press. - 2211-1247. ; 14:12, s. 2988-3000
  • Tidskriftsartikel (refereegranskat)abstract
    • To gain insights into the regulatory mechanisms of hematopoietic stem cells (HSCs), we employed a genome-wide RNAi screen in human cord-blood derived cells and identified candidate genes whose knockdown maintained the HSC phenotype during culture. A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon individual validation of these cohesin genes, we found that their knockdown led to an immediate expansion of cells with an HSC phenotype in vitro. A similar expansion was observed in vivo following transplantation to immunodeficient mice. Transcriptome analysis of cohesin-deficient CD34(+) cells showed an upregulation of HSC-specific genes, demonstrating an immediate shift toward a more stem-cell-like gene expression signature upon cohesin deficiency. Our findings implicate cohesin as a major regulator of HSCs and illustrate the power of global RNAi screens to identify modifiers of cell fate.
25.
  • Harbst, Katja, et al. (författare)
  • Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma
  • 2016
  • Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 0008-5472. ; 76:16, s. 4765-4774
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P <0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome.
  •  
26.
27.
  • Ju, Young Seok, et al. (författare)
  • Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.
  • 2015
  • Ingår i: Genome Research. - Cold Spring Harbor Laboratory Press. - 1549-5469. ; 25:6, s. 814-824
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.
28.
  • Ju, Young Seok, et al. (författare)
  • Somatic mutations reveal asymmetric cellular dynamics in the early human embryo
  • 2017
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836. ; 543:7647, s. 714-718
  • Tidskriftsartikel (refereegranskat)abstract
    • Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
  •  
29.
  • Karlsson, Anna K, et al. (författare)
  • Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.
  • 2015
  • Ingår i: Oncotarget. - Impact Journals, LLC. - 1949-2553. ; 6:26, s. 22028-22037
  • Tidskriftsartikel (refereegranskat)abstract
    • Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.
30.
  • Kiiski, Johanna I., et al. (författare)
  • FANCM mutation c.5791C&gt;T is a risk factor for triple-negative breast cancer in the Finnish population
  • 2017
  • Ingår i: Breast Cancer Research and Treatment. - Springer. - 0167-6806. ; 166:1, s. 217-226
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The FANCM c.5101C>T nonsense mutation was previously found to associate with breast cancer in the Finnish population, especially among triple-negative cases. Here, we studied the prevalence of three other FANCM variants: c.5791C>T, which has been reported to predispose to familial breast cancer, and the c.4025_4026delCT and c.5293dupA variants recently identified in Finnish cancer patients. Methods: We genotyped the FANCM c.5791C>T mutation in 4806 invasive breast cancer patients, including BRCA1/2 mutation negative familial cases and unselected cases, and in 2734 healthy population controls from four different geographical areas of Finland. The association of the mutation with breast cancer risk among patient subgroups was statistically evaluated. We further analyzed the combined risk associated with c.5101C>T and c.5791C>T mutations. We also genotyped 526 unselected ovarian cancer patients for the c.5791C>T mutation and 862 familial breast cancer patients for the c.4025_4026delCT and c.5293dupA variants. Results: The frequency of the FANCM c.5791C>T mutation was higher among breast cancer cases than in controls (OR 1.94, 95% CI 0.87–4.32, P = 0.11), with a statistically significant association with triple-negative breast cancer (OR 5.14, 95% CI 1.65–16.0, P = 0.005). The combined analysis for c.5101C>T and c.5791C>T carriers confirmed a strong association with breast cancer (OR 1.86, 95% CI 1.32–2.49, P = 0.0002), especially among the triple-negative patients (OR 3.08, 95% CI 1.77–5.35, P = 0.00007). For the other variants, only one additional c.4025_4026delCT carrier and no c.5293dupA carriers were observed. Conclusions: These results support the role of FANCM as a breast cancer susceptibility gene, particularly for triple-negative breast cancer.
Skapa referenser, mejla, bekava och länka
  • Resultat 21-30 av 70
  • Föregående 12[3]4567Nästa
Åtkomst
fritt online (43)
Typ av publikation
tidskriftsartikel (60)
konferensbidrag (8)
annan publikation (1)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (67)
övrigt vetenskapligt (10)
Författare/redaktör
Borg, Åke, (68)
Loman, Niklas, (18)
Vallon-Christersson, ... (18)
Rydén, Lisa, (17)
Ehinger, Anna, (17)
Saal, Lao, (16)
visa fler...
Häkkinen, Jari, (15)
Larsson, Christer, (14)
Staaf, Johan, (13)
Kvist, Anders (13)
Bendahl, Pär Ola, (10)
Törngren, Therese, (9)
Olsson, Håkan, (8)
Borg, A, (7)
Nik-Zainal, Serena (7)
Chen, Yilun, (7)
Jönsson, Göran B, (7)
Børresen-Dale, Anne- ... (6)
Nevanlinna, Heli (6)
Stratton, Michael R. (6)
Martin, Sancha (6)
Ramakrishna, Manasa (6)
Richardson, Andrea L ... (6)
Campbell, Peter J. (6)
Brueffer, Christian, (6)
Winter, Christof, (6)
Gerdes, Anne-Marie (6)
Hansen, Thomas V. O. (6)
Frisen, Jonas (6)
Salmen, Fredrik, (6)
Aittomäki, Kristiina (5)
Lundeberg, Joakim, (5)
Benitez, Javier (5)
Davies, Helen R. (5)
Lakhani, Sunil R. (5)
Span, Paul N. (5)
Gruvberger, Sofia, (5)
Grabau, Dorthe, (5)
Thomassen, Mads (5)
Ehrencrona, Hans (5)
Wappenschmidt, Barba ... (5)
Arnold, Norbert (5)
Nathanson, Katherine ... (5)
Manoukian, Siranoush (5)
Radice, Paolo (5)
Diez, Orland (5)
Borg, Ake (5)
Ingvar, Christian, (5)
Vickovic, Sanja, (5)
Martens, John W. M. (5)
visa färre...
Lärosäte
Lunds universitet (67)
Karolinska Institutet (11)
Uppsala universitet (7)
Umeå universitet (2)
Kungliga Tekniska Högskolan (2)
Stockholms universitet (2)
visa fler...
Linköpings universitet (2)
Göteborgs universitet (1)
Örebro universitet (1)
Naturhistoriska riksmuseet (1)
visa färre...
Språk
Engelska (69)
Svenska (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (66)
Naturvetenskap (6)
Teknik (3)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy