CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate

被引：131

作者：

Stolarova, Lenka ^{[1
,2
]}

Kleiblova, Petra ^{[3
,4
]}

Janatova, Marketa ^{[1
]}

Soukupova, Jana ^{[1
]}

Zemankova, Petra ^{[1
]}

Macurek, Libor ^{[2
]}

Kleibl, Zdenek ^{[1
]}

机构：

[1] Charles Univ Prague, Fac Med 1, Inst Biochem & Expt Oncol, Prague 12800, Czech Republic

[2] Czech Acad Sci, Inst Mol Genet, Lab Canc Cell Biol, Prague 14220, Czech Republic

[3] Charles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Prague 12800, Czech Republic

[4] Gen Univ Hosp Prague, Prague 12800, Czech Republic

来源：

CELLS | 2020年 / 9卷 / 12期

关键词：

checkpoint kinase 2; CHK2; CHEK2; KAP1; WIP1; germline mutation; hereditary cancer; breast cancer; prostate cancer; renal cancer; thyroid cancer; colorectal cancer; DNA-DAMAGE CHECKPOINT; COMPREHENSIVE RESEARCH SYNOPSIS; CHEK2-POSITIVE BREAST CANCERS; PROTEIN-TRUNCATING VARIANTS; P53-MEDIATED G(1) ARREST; CHK2; TUMOR-SUPPRESSOR; COLORECTAL-CANCER; SUSCEPTIBILITY GENES; HEREDITARY BREAST; INCREASED RISK;

D O I：

10.3390/cells9122675

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Germline alterations in many genes coding for proteins regulating DNA repair and DNA damage response (DDR) to DNA double-strand breaks (DDSB) have been recognized as pathogenic factors in hereditary cancer predisposition. The ATM-CHEK2-p53 axis has been documented as a backbone for DDR and hypothesized as a barrier against cancer initiation. However, although CHK2 kinase coded by the CHEK2 gene expedites the DDR signal, its function in activation of p53-dependent cell cycle arrest is dispensable. CHEK2 mutations rank among the most frequent germline alterations revealed by germline genetic testing for various hereditary cancer predispositions, but their interpretation is not trivial. From the perspective of interpretation of germline CHEK2 variants, we review the current knowledge related to the structure of the CHEK2 gene, the function of CHK2 kinase, and the clinical significance of CHEK2 germline mutations in patients with hereditary breast, prostate, kidney, thyroid, and colon cancers.

引用

页数：43

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