Two co-existing germline mutations P53 V157D and PMS2 R20Q promote tumorigenesis in a familial cancer syndrome.

Wang Z, Sun Y, Gao B, Lu Y, Fang R, Gao Y, Xiao T, Liu XY, Pao W, Zhao Y, Chen H, Ji H
Cancer Lett. 2014 342 (1): 36-42

PMID: 23981578 · PMCID: PMC3981830 · DOI:10.1016/j.canlet.2013.08.032

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.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

MeSH Terms (28)

Adenocarcinoma Adenosine Triphosphatases Adult Animals Animals, Genetically Modified Base Sequence Carcinogenesis Cell Line DNA-Binding Proteins DNA Mutational Analysis DNA Repair Enzymes Drosophila Female Genetic Association Studies Genetic Predisposition to Disease Germ-Line Mutation Humans Lung Neoplasms Male Mice Middle Aged Mismatch Repair Endonuclease PMS2 Mutation, Missense Neoplastic Syndromes, Hereditary Pedigree Radiography Tumor Suppressor Protein p53 Young Adult

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