CHEK2 variants: linking functional impact to cancer risk

Matsuoka, 1998, Linkage of ATM to cell cycle regulation by the Chk2 protein kinase, Science, 282, 1893, 10.1126/science.282.5395.1893 Chehab, 2000, Chk2/hCds1 functions as a DNA damage checkpoint in G1 by stabilizing p53, Genes Dev., 14, 278, 10.1101/gad.14.3.278 Bell, 1999, Heterozygous germ line hCHK2 mutations in Li–Fraumeni syndrome, Science, 286, 2528, 10.1126/science.286.5449.2528 Schneider, 1999, Li–Fraumeni syndrome, GeneReviews McBride, 2014, Li–Fraumeni syndrome: cancer risk assessment and clinical management, Nat. Rev. Clin. Oncol., 11, 260, 10.1038/nrclinonc.2014.41 Breast Cancer Association Consortium, 2021, Breast cancer risk genes – association analysis in more than 113,000 women, N. Engl. J. Med., 384, 428, 10.1056/NEJMoa1913948 Couch, 2017, Associations between cancer predisposition testing panel genes and breast cancer, JAMA Oncol., 3, 1190, 10.1001/jamaoncol.2017.0424 Decker, 2017, Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks, J. Med. Genet., 54, 7327, 10.1136/jmedgenet-2017-104588 Hauke, 2018, Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer, Cancer Med., 7, 1349, 10.1002/cam4.1376 Meijers-Heijboer, 2002, Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations, Nat. Genet., 31, 555 Weischer, 2007, Increased risk of breast cancer associated with CHEK2*1100delC, J. Clin. Oncol., 25, 57, 10.1200/JCO.2005.05.5160 Cybulski, 2004, CHEK2 is a multiorgan cancer susceptibility gene, Am. J. Hum. Genet., 75, 1131, 10.1086/426403 Stolarova, 2020, CHEK2 germline variants in cancer predisposition: stalemate rather than checkmate, Cells, 9, 2675, 10.3390/cells9122675 Landrum, 2014, ClinVar: public archive of relationships among sequence variation and human phenotype, Nucleic Acids Res., 42, D980, 10.1093/nar/gkt1113 Brnich, 2019, Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework, Genome Med, 12, 3, 10.1186/s13073-019-0690-2 Bell, 2007, Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts, Int. J. Cancer, 121, 2661, 10.1002/ijc.23026 Boonen, 2022, Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk, Cancer Res., 82, 615, 10.1158/0008-5472.CAN-21-1845 Chrisanthar, 2008, CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer, PLoS One, 3, 10.1371/journal.pone.0003062 Cuella-Martin, 2021, Functional interrogation of DNA damage response variants with base editing screens, Cell, 184, 1081, 10.1016/j.cell.2021.01.041 Delimitsou, 2019, Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system, Hum. Mutat., 40, 631, 10.1002/humu.23728 Falck, 2001, The ATM–Chk2–Cdc25A checkpoint pathway guards against radioresistant DNA synthesis, Nature, 410, 842, 10.1038/35071124 Kleiblova, 2019, Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer, Int. J. Cancer, 145, 1782, 10.1002/ijc.32385 Lee, 2001, Destabilization of CHK2 by a missense mutation associated with Li–Fraumeni Syndrome, Cancer Res., 61, 8062 Roeb, 2012, Response to DNA damage of CHEK2 missense mutations in familial breast cancer, Hum. Mol. Genet., 21, 2738, 10.1093/hmg/dds101 Shaag, 2005, Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population, Hum. Mol. Genet., 14, 555, 10.1093/hmg/ddi052 Tischkowitz, 2008, Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer, Cancer Lett., 270, 173, 10.1016/j.canlet.2008.05.006 Wang, 2015, A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast cancer patients impairs its activity and is associated with increased breast cancer risk, Oncogene, 34, 5198, 10.1038/onc.2014.443 Wu, 2001, Characterization of tumor-associated Chk2 mutations, J. Biol. Chem., 276, 2971, 10.1074/jbc.M009727200 Ahn, 2004, The Chk2 protein kinase, DNA Repair (Amst), 3, 1039, 10.1016/j.dnarep.2004.03.033 Bartek, 2003, Chk1 and Chk2 kinases in checkpoint control and cancer, Cancer Cell, 3, 421, 10.1016/S1535-6108(03)00110-7 Kastan, 2004, Cell-cycle checkpoints and cancer, Nature, 432, 316, 10.1038/nature03097 Li, 2002, Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2, Mol. Cell, 9, 1045, 10.1016/S1097-2765(02)00527-0 Zhang, 2004, Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair, Mol. Cell. Biol., 24, 708, 10.1128/MCB.24.2.708-718.2004 Hu, 2012, Roles of Kruppel-associated box (KRAB)-associated co-repressor KAP1 Ser-473 phosphorylation in DNA damage response, J. Biol. Chem., 287, 18937, 10.1074/jbc.M111.313262 Lanz, 2019, DNA damage kinase signaling: checkpoint and repair at 30 years, EMBO J., 38, 10.15252/embj.2019101801 Zhao, 2001, The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage, EMBO J., 20, 3544, 10.1093/emboj/20.13.3544 Matreyek, 2018, Multiplex assessment of protein variant abundance by massively parallel sequencing, Nat. Genet., 50, 874, 10.1038/s41588-018-0122-z Boonen, 2019, Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2, Nat. Commun., 10, 5296, 10.1038/s41467-019-13194-2 Bartek, 2001, CHK2 kinase – a busy messenger, Nat. Rev. Mol. Cell Biol., 2, 877, 10.1038/35103059 Findlay, 2018, Accurate classification of BRCA1 variants with saturation genome editing, Nature, 562, 217, 10.1038/s41586-018-0461-z Parsons, 2019, Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification, Hum. Mutat., 40, 1557, 10.1002/humu.23818 Caputo, 2021, Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: a powerful approach, Am. J. Hum. Genet., 108, 1907, 10.1016/j.ajhg.2021.09.003 Michailidou, 2017, Association analysis identifies 65 new breast cancer risk loci, Nature, 551, 92, 10.1038/nature24284 Southey, 2016, PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS, J. Med. Genet., 53, 800, 10.1136/jmedgenet-2016-103839 Boonen, 2021, Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk, Cancer Res., 82, 615, 10.1158/0008-5472.CAN-21-1845 Heijl, 2020, Mind the gap: preventing circularity in missense variant prediction, BioRxiv Vroling, 2021, White paper: the helix pathogenicity prediction platform, ArXiv Miosge, 2015, Comparison of predicted and actual consequences of missense mutations, Proc. Natl. Acad. Sci. U. S. A., 112, E5189, 10.1073/pnas.1511585112 Rodrigue, 2019, A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor, Nucleic Acids Res., 47, 10662, 10.1093/nar/gkz780 Starita, 2018, A multiplex homology-directed DNA repair assay reveals the impact of more than 1,000 BRCA1 missense substitution variants on protein function, Am. J. Hum. Genet., 103, 498, 10.1016/j.ajhg.2018.07.016