Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing
Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1172365/full |
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| author | An-Ko Chung An-Ko Chung Ro-Ting Lin Chun-Chieh Yeh Chun-Chieh Yeh Chi-Ying Yang Chang-Jiun Wu Pei-Lung Chen Pei-Lung Chen Jaw-Town Lin |
| author_facet | An-Ko Chung An-Ko Chung Ro-Ting Lin Chun-Chieh Yeh Chun-Chieh Yeh Chi-Ying Yang Chang-Jiun Wu Pei-Lung Chen Pei-Lung Chen Jaw-Town Lin |
| author_sort | An-Ko Chung |
| collection | DOAJ |
| description | Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected. |
| first_indexed | 2024-04-09T13:30:13Z |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T13:30:13Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-f5cc4d3912b64799b3537a8988881fa22023-05-10T04:45:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-05-011410.3389/fgene.2023.11723651172365Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencingAn-Ko Chung0An-Ko Chung1Ro-Ting Lin2Chun-Chieh Yeh3Chun-Chieh Yeh4Chi-Ying Yang5Chang-Jiun Wu6Pei-Lung Chen7Pei-Lung Chen8Jaw-Town Lin9Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, TaiwanSchool of Medicine, China Medical University, Taichung, TaiwanDepartment of Surgery, China Medical University Hospital, Taichung, TaiwanDepartment of Internal Medicine, Digestive Medicine Center, China Medical University Hospital, Taichung, TaiwanDepartment of Genomic Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX, United StatesGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, TaiwanDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, TaiwanIdentification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected.https://www.frontiersin.org/articles/10.3389/fgene.2023.1172365/fullpancreatic ductal adenocarcinoma (PADC)whole genome sequencing (WGS)germline genetic testingstructural variant (SV)cancer genetic |
| spellingShingle | An-Ko Chung An-Ko Chung Ro-Ting Lin Chun-Chieh Yeh Chun-Chieh Yeh Chi-Ying Yang Chang-Jiun Wu Pei-Lung Chen Pei-Lung Chen Jaw-Town Lin Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing Frontiers in Genetics pancreatic ductal adenocarcinoma (PADC) whole genome sequencing (WGS) germline genetic testing structural variant (SV) cancer genetic |
| title | Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| title_full | Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| title_fullStr | Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| title_full_unstemmed | Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| title_short | Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| title_sort | diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing |
| topic | pancreatic ductal adenocarcinoma (PADC) whole genome sequencing (WGS) germline genetic testing structural variant (SV) cancer genetic |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1172365/full |
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