title: Two co-existing germline mutations P53 V157D and PMS2 R20Q promote tumorigenesis in a familial cancer syndrome.
abstract: Germline mutations are responsible for familial cancer syndromes which account for approximately 5-10% of all types of cancers. These mutations mainly occur at tumor suppressor genes or genome stability genes, such as DNA repair genes. Here we have identified a cancer predisposition family, in which eight members were inflicted with a wide spectrum of cancer including one diagnosed with lung cancer at 22years old. Sequencing analysis of tumor samples as well as histologically normal specimens identified two germline mutations co-existing in the familial cancer syndrome, the mutation of tumor suppressor gene P53 V157D and mismatch repair gene PMS2 R20Q. We further demonstrate that P53 V157D and/or PMS2 R20Q mutant promotes lung cancer cell proliferation. These two mutants are capable of promoting colony formation in soft agar as well as tumor formation in transgenic drosophila system. Collectively, these data have uncovered the important role of co-existing germline P53 and PMS2 mutations in the familial cancer syndrome development.
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Zuoyun
authors: Z
authors: Wang
authors: Yihua
authors: Y
authors: Sun
authors: Bin
authors: B
authors: Gao
authors: Yi
authors: Y
authors: Lu
authors: Rong
authors: R
authors: Fang
authors: Yijun
authors: Y
authors: Gao
authors: Tian
authors: T
authors: Xiao
authors: Xin-Yuan
authors: XY
authors: Liu
authors: William
authors: W
authors: Pao
authors: Yun
authors: Y
authors: Zhao
authors: Haiquan
authors: H
authors: Chen
authors: Hongbin
authors: H
authors: Ji
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000601:surgery; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics*; D002460:Cell Line; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000601:surgery; D008297:Male; D051379:Mice; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D020125:Mutation, Missense; D009386:Neoplastic Syndromes, Hereditary / Q000000981:diagnostic imaging* / Q000235:genetics / Q000601:surgery; D010375:Pedigree; D011859:Radiography; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes
keywords: Co-existing; Familial cancer syndrome; Germline mutation; P53 V157D; PMS2 R20Q
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