| 1. |
- Cini, Giulia, et al.
(författare)
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Lynch syndrome and Muir-Torre phenotype associated with a recurrent variant in the 3 ' UTR of the MSH6 gene
- 2021
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762 .- 2210-7770. ; 254, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- A MSH6 3'UTR variant (c.*23_26dup) was found in 13 unrelated families consulted for Lynch/Muir-Torre Syndrome. This variant, which is very rare in the genomic databases, was absent in healthy controls and strongly segregated with the disease in the studied pedigrees. All tumors were defective for MSH2/MSH6/MSH3 proteins expression, but only MSH2 somatic pathogenic mutations were found in 5 of the 12 sequenced tumors. Moreover, we had no evidence of MSH6 transcript decrease in carriers, whereas MSH2 transcript was downregulated. Additional evaluations performed in representative carriers, including karyotype, arrayCGH and Linked-Reads whole genome sequencing, failed to evidence any MSH2 germline pathogenic variant. Posterior probability of pathogenicity for MSH6 c.*23_26dup was obtained from a multifactorial analysis incorporating segregation and phenotypic data and resulted >0.999, allowing to classify the variant as pathogenic (InSiGHT Class 5). Carriers shared a common haplotype involving MSH2/MSH6 loci, then a cryptic disease-associated variant, linked with MSH6 c.*23_26dup, cannot be completely excluded. Even if it is not clear whether the MSH6 variant is pathogenic per se or simply a marker of a disease-associated MSH2/MSH6 haplotype, all data collected on patients and pedigrees prompted us to manage the variant as pathogenic and to offer predictive testing within these families.
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| 2. |
- Köster, Jan, et al.
(författare)
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Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development
- 2020
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Ingår i: Cancer Genetics. - : ELSEVIER SCIENCE INC. - 2210-7762 .- 2210-7770. ; 241, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.
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| 3. |
- Tuominen, Rainer, et al.
(författare)
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Investigation of a putative melanoma susceptibility locus at chromosome 3q29
- 2014
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Ingår i: Cancer Genetics. - : Elsevier. - 2210-7762 .- 2210-7770. ; 207:3, s. 70-74
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.
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| 4. |
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| 5. |
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| 6. |
- Kristoffersson, U., et al.
(författare)
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Fine needle aspiration biopsy: A useful tool in tumor cytogenetics with special reference to malignant lymphomas
- 1981
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Ingår i: Cancer Genetics and Cytogenetics. - 2210-7762. ; 4:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- A method for chromosome analysis of malignant cells by means of fine needle aspiration biopsy has been developed. The method has some obvious advantages compared to conventional surgical biopsy. During a 1-year period 25 consecutive non-Hodgkin, non-Burkitt lymphoma biopsies from 19 patients have been studied. In 14 out of 21 lymph node biopsies chromosome analysis was successful; whereas, four biopsies of subcutaneous lymphomas were unsuccessful. © 1981.
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| 7. |
- Mandahl, Nils, et al.
(författare)
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HMGA2 and MDM2 expression in lipomatous tumors with partial, low-level amplification of sequences from the long arm of chromosome 12.
- 2011
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 204:10, s. 550-556
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Tidskriftsartikel (refereegranskat)abstract
- Ordinary lipomas are cytogenetically characterized primarily by simple balanced chromosome aberrations with stable morphologies, most of which affect chromosome segment, 12q13-15, where the HMGA2 gene plays a key pathogenetic role. Atypical lipomatous tumors (ALTs) display supernumerary ring or giant marker chromosomes with amplification of several genes including HMGA2 and MDM2. A study of HMGA2 expression in a variety of adipocytic tumors showed aberrant expression in lipomas with 12q13-15 aberrations and ring chromosomes as well as in ALTs and well-differentiated liposarcomas (WDLSs), and frequent differential expression of HMGA2 exons 1-2 versus that of exons 4-5. A minor subset of adipocytic tumors harbors unbalanced karyotypes with extra copies of 12q sequences in structures that are not giant marker or ring chromosomes. Out of a series of ten such tumors, three lipomas and four ALTs with more than two copies of 12q13-15 and breakpoints in 12q13-15 could be analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) to find out whether HMGA2 and MDM2 expression was more similar to the levels seen in lipomas with cytogenetically balanced aberrations of 12q13-15, or to ALTs with giant ring or marker chromosomes. One of two ALTs with more complex, hyperdiploid karyotypes had expression levels closer to those seen in ALT, whereas the remaining six cases were similar to lipomas with 12q13-15 changes and ring chromosomes. Differential expression was seen in two ALTs and all three lipomas. Two cases showed MDM2 expression levels similar to those found among WDLSs, two cases showed levels similar to those found among lipomas, whereas the remaining three cases displayed intermediate expression levels. The studied cases represent intermediates between lipoma and ALT, insofar as they shared 12q13-15 rearrangements and karyotypic stability with lipomas and gain of 12q sequences with ALTs. Neither of these characteristics can be used to discriminate between lipoma and ALT.
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| 8. |
- Mertens, Fredrik, et al.
(författare)
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The MDM2 SNP309 G allele is not preferentially amplified in bone and soft tissue tumors.
- 2012
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 205:9, s. 470-473
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Tidskriftsartikel (refereegranskat)abstract
- The transcriptional enhancer region in intron 1 of the proto-oncogene MDM2 contains a polymorphic site (SNP309) that may harbor a G or a T nucleotide. Previous studies have shown that the G allele confers a higher affinity for the Sp1 transcription factor, resulting in an increased transcriptional activity of MDM2. A constitutional G allele has also been associated with earlier onset of various cancer types, and studies of sarcomas have shown an enrichment of the G allele in tumors with MDM2 amplification, notably atypical lipomatous tumor (also known as well-differentiated liposarcoma). In the present study, we analyzed the SNP309 genotype in blood samples and tumor tissue from 57 patients with bone or soft tissue tumors showing amplification of MDM2. We did not observe any constitutional enrichment of the G allele. More importantly, there was no preferential amplification of the G allele in tumor tissue from TG heterozygotes. The expression levels of MDM2 messenger RNA were not higher in tumors with amplification of the G allele than in tumors with amplification of the T allele. Thus, we could not find any evidence for a selective advantage of the SNP309 G allele in bone and soft tissue tumors with MDM2 amplification.
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| 9. |
- Mohajeri, Arezoo, et al.
(författare)
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SNP array and FISH findings in two pleomorphic hyalinizing angiectatic tumors.
- 2012
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 205:12, s. 6-673
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Tidskriftsartikel (refereegranskat)abstract
- Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare soft tissue tumor of intermediate malignancy and uncertain cellular origin and lineage of differentiation. Although PHAT is still poorly characterized at the genetic level, there is a potential genetic overlap with two other soft tissue tumors: myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT); MIFS and HFLT share a characteristic t(1;10)(p22;q24) with breakpoints in the TGFBR3 locus on chromosome 1 and near the MGEA5 locus on chromosome 10. Recently, a PHAT with a similar t(1;10) was reported, suggesting a genetic link between MIFS/HFLT and PHAT. To ascertain whether PHAT is also associated with this translocation, two cases were subjected to single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization analyses. Neither PHAT showed a t(1;10) or other types of rearrangement of the TGFBR3 or MGEA5 loci. Both tumors showed imbalances in the SNP array analysis, but none was shared. Thus, the results indicate that PHAT is genetically distinguishable from MIFS and HFLT, but further studies are needed to identify the salient genetic pathways involved in PHAT development.
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| 10. |
- Niini, Tarja, et al.
(författare)
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Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study
- 2012
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 205:11, s. 588-593
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Tidskriftsartikel (refereegranskat)abstract
- Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.
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