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: Zuoyun Wang, Yihua Sun, Bin Gao, Yi Lu, Rong Fang, Yijun Gao, Tian Xiao, Xin-Yuan Liu, William Pao, Yun Zhao, Haiquan Chen, Hongbin Ji
• Journal: Cancer letters (Cancer Lett) Vol. 342 Issue 1 Pg. 36-42 (Jan 01 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23981578 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• DNA-Binding Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• Adenosine Triphosphatases
• PMS2 protein, human
• Mismatch Repair Endonuclease PMS2
• DNA Repair Enzymes

Topics

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