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Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors
Author(s) -
Miller Carl W.,
Ikezoe Takayuki,
Krug Utz,
Hofmann WolfK.,
Tavor Sigal,
Vegesna Vijaya,
Tsukasaki Kunihiro,
Takeuchi Seisho,
Koeffler H. Phillip
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1207
Subject(s) - cancer research , checkpoint kinase 2 , ovarian cancer , stk11 , biology , dna damage , mutation , exon , tumor suppressor gene , cancer , germline mutation , gene , cell cycle checkpoint , carcinogenesis , genetics , cell cycle , dna , kras
Abstract Checkpoint genes, activated in response to DNA damage and other stresses, are frequently targeted for alteration in cancer. Checkpoint kinase 2 ( CHK2, CDS1, RAD53 ) is activated by ataxia telangiectasia mutated (ATM) in response to γ irradiation. Activated CHK2 stabilizes TP53, and acts on other cell cycle and stress regulators. These findings place CHK2 in the middle of a pathway frequently targeted in cancer. Because of this, and the observation that CHK2 mutations are inherited in some Li‐Fraumeni cancer syndrome families, we decided to examine the role of CHK2 mutations in sporadic cancers. Exploiting the genomic sequence of chromosome 22, we looked for mutations in the exons and intron junctions of the CHK2 gene in DNA samples from 170 patients (57 osteosarcomas, 25 other sarcomas, 35 nonsmall‐cell lung, 20 ovarian, and 33 breast cancers). Missense mutations affecting the forkhead and kinase domains were detected in four osteosarcomas and in one ovarian and one lung cancer. These findings of CHK2 gene mutations are consistent with osteosarcoma being a defining tumor of Li‐Fraumeni syndrome. The occurrence of CHK2 mutations in sporadic cancers emphasizes the importance of the stress pathway which includes TP53.