title: A Novel WRN Frameshift Mutation Identified by Multiplex Genetic Testing in a Family with Multiple Cases of Cancer.
abstract: Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2. Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China; Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, P. R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Beilun Branch of First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, Zhejiang, P. R. China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang, P. R. China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang, P. R. China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shen
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang, P. R. China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang, P. R. China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D053487:DEAD-box RNA Helicases / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D015723:Gene Library; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D053484:RecQ Helicases / Q000737:chemistry / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics; D017422:Sequence Analysis, DNA; D000071657:Werner Syndrome Helicase
chemical_list: C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D005090:Exodeoxyribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D053487:DEAD-box RNA Helicases