Whole genome sequencing identifies rare germline variants enriched in cancer related genes in firstdegree relatives of familial pancreatic cancer patients
| العنوان: | Whole genome sequencing identifies rare germline variants enriched in cancer related genes in firstdegree relatives of familial pancreatic cancer patients |
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| المؤلفون: | Michael Bau Mortensen, Sönke Detlefsen, Ove B. Schaffalitzky de Muckadell, Maiken Thyregod Joergensen, Ming Tan, Klaus Brusgaard, Anne-Marie Gerdes |
| المصدر: | Tan, M, Brusgaard, K, Gerdes, A M, Mortensen, M B, Detlefsen, S, Schaffalitzky de Muckadell, O B & Joergensen, M T 2021, ' Whole genome sequencing identifies rare germline variants enriched in cancer related genes in firstdegree relatives of familial pancreatic cancer patients ', Clinical Genetics, vol. 100, no. 5, pp. 551-562 . https://doi.org/10.1111/cge.14038 Tan, M, Brusgaard, K, Gerdes, A-M A, Mortensen, M B, Detlefsen, S, Schaffalitzky, O B & Jørgensen, M T 2021, ' Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first-degree relatives of familial pancreatic cancer patients ', United European Gastroenterology Journal, vol. 9, no. 8 Suppl., P0836, pp. 751-752 . https://doi.org/10.1002/ueg2.12144 Tan, M, Brusgaard, K, Gerdes, A-M A, Mortensen, M B, Detlefsen, S, Schaffalitzky, O B & Jørgensen, M T 2021, ' Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients ', Clinical Genetics, vol. 100, no. 5, pp. 551-562 . https://doi.org/10.1111/cge.14038 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, False discovery rate, Genotype, Denmark, familial pancreatic cancer, Biology, Polymorphism, Single Nucleotide, Germline, first-degree relatives, rare germline variants, Germline mutation, Biomarkers, Tumor, Genetics, Humans, Family, Genetic Predisposition to Disease, First-degree relatives, Gene, Alleles, Genetic Association Studies, Germ-Line Mutation, Genetics (clinical), Aged, Genetic association, Aged, 80 and over, Whole genome sequencing, whole genome sequencing, cancer genes, Whole Genome Sequencing, Carcinoma, Family aggregation, Oncogenes, Sequence Analysis, DNA, Middle Aged, Pedigree, Pancreatic Neoplasms, Female |
| الوصف: | First-degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk-assessment and management of high-risk individuals. Using a Danish cohort of 27 FPC families, we performed whole-genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer-related genes and cancer-driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes were enriched by gene clusters encoding for extracellular matrix and associated proteins. PTV genes were over-represented by functions related to transport of small molecules, innate immune system, ion channel transport, and stimuli-sensing channels. In conclusion, FDRs of FPC patients carry rare germline variants related to cancer pathogenesis that may contribute to increased susceptibility to PDAC. The identified variants may potentially be useful for risk prediction of high-risk individuals in predisposed families. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1111/cge.14038 |
| DOI: | 10.1002/ueg2.12144 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::304b2de7f3aa7ec00da3d3b8c31fdc2f https://curis.ku.dk/ws/files/304068257/Clinical_Genetics_2021_Tan_Whole_genome_sequencing_identifies_rare_germline_variants_enriched_in_cancer_related_genes.pdf |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....304b2de7f3aa7ec00da3d3b8c31fdc2f |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1111/cge.14038 |
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