Germline mutations in homologous recombination repair genes among Chinese pancreatic ductal adenocarcinoma patients detected using next-generation sequencing. 2023

Huiqin Jiang, and Fei Huang, and Xinning Chen, and Li Zhang, and Minna Shen, and Baishen Pan, and Beili Wang, and Wei Guo
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Genetic testing for pancreatic ductal adenocarcinoma (PDAC) patients is in constant development. However, the status of homologous recombination repair (HRR) genes in unselected Chinese PDAC has not been fully explored. This study aims to characterize the profile of germline mutations in HRR genes in Chinese PDAC patients. A cohort of 256 PDAC patients were enrolled at Zhongshan Hospital Fudan University between 2019 and 2021. Germline DNA was analyzed by next-generation sequencing using a multigene panel of the 21 HRR genes. The germline pathogenic (P)/likely pathogenic (LP) variant rates were 7.0% (18/256) in unselected patients with pancreatic cancer. Among them, 1.6% (4/256) were identified as harboring BRCA2 variants, and 5.5% (14/256) patients carried non-BRCA variants. Variants were detected in eight non-BRCA genes, including ATM (4, 1.6%), PALB2 (4, 1.6%), ATR (1, 0.4%), BRIP1 (1, 0.4%), CHEK2 (1, 0.4%), MRE11 (1, 0.4%), PTEN (1, 0.4%), and STK11 (1, 0.4%). ATM, BRCA2, and PALB2 were the most prevalent variant genes. If only BRCA1/2 was tested, 5.5% of P/LP variants would have been lost. Further, we found that the landscape of P/LP HRR variants in various population cohorts was quite different. However, no significant difference was found in clinical characteristics between germline HRR P/LP carriers and non-carriers. In our study, one case carrying a germline PALB2 variant showed a long-time response to platinum-based chemotherapy and PARP inhibitor. This study comprehensively depicts the prevalence and characteristics of germline HRR mutations in unselected Chinese PDAC patients. Our findings show the clinical utility of a multigene panel may increase the detection of P/LP HRR carriers.

UI MeSH Term Description Entries
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000095225 East Asian People East Asians,Eastern Asian People,Eastern Asians,Far East Asians,Chinese,Japanese,Koreans,Asian People, East,Asian People, Eastern,Asian, East,Asian, Eastern,Asian, Far East,East Asian,East Asian Peoples,Eastern Asian,Eastern Asian Peoples,Far East Asian,People, East Asian,People, Eastern Asian
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation
D059767 Recombinational DNA Repair Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids. Homologous Recombination DNA Repair,Homologous Recombination Repair of DNA,Homology-Directed dsDNA Break Repair,Homologous Recombination Double-Stranded Break DNA Repair,Homologous Recombination Repair,Homologous Recombinational Repair,Recombination Repair,Recombinational Repair of DNA,DNA Recombinational Repair,DNA Repair, Recombinational,Homologous Recombination Double Stranded Break DNA Repair,Homologous Recombinational Repairs,Homology Directed dsDNA Break Repair,Recombination Repair, Homologous,Recombinational Repair, Homologous,Repair, Homologous Recombinational,Repair, Recombination,Repair, Recombinational DNA
D018095 Germ-Line Mutation Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. Mutation, Germ-Line,Germline Mutation,Germ Line Mutation,Germ-Line Mutations,Germline Mutations,Mutation, Germ Line,Mutation, Germline,Mutations, Germ-Line,Mutations, Germline
D019313 BRCA1 Protein The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91) BRCA1 Gene Product,Breast Cancer 1 Gene Product,Breast Cancer 1 Protein,Breast Cancer Type 1 Susceptibility Protein,Ring Finger Protein 53
D021441 Carcinoma, Pancreatic Ductal Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS. Pancreatic Ductal Carcinoma,Carcinoma, Ductal, Pancreatic,Duct-Cell Carcinoma of the Pancreas,Duct-Cell Carcinoma, Pancreas,Ductal Carcinoma of the Pancreas,Pancreatic Duct Cell Carcinoma,Carcinoma, Pancreas Duct-Cell,Carcinomas, Pancreas Duct-Cell,Carcinomas, Pancreatic Ductal,Duct Cell Carcinoma of the Pancreas,Duct Cell Carcinoma, Pancreas,Duct-Cell Carcinomas, Pancreas,Ductal Carcinoma, Pancreatic,Ductal Carcinomas, Pancreatic,Pancreas Duct-Cell Carcinoma,Pancreas Duct-Cell Carcinomas,Pancreatic Ductal Carcinomas
D024682 BRCA2 Protein A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6) Breast Cancer 2 Gene Product,Fanconi Anemia Complementation Group D1 Protein,BRCA2 Gene Product,Breast Cancer 2 Protein,FANCD1 Protein,Fanconi Anemia Group D1 Complementing Protein,Fanconi Anemia Group D1 Protein

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