GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2): Difference between revisions
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|ATM; Inactivating mutations | |ATM; Inactivating mutations | ||
|DNA damage sensing and signaling (ATM–CHK2 pathway) | |DNA damage sensing and signaling (ATM–CHK2 pathway) | ||
|Impaired activation of DNA damage checkpoints, defective response to double-strand breaks, accumulation of genomic damage, and cancer predisposition | |Impaired activation of DNA damage checkpoints, defective response to double-strand breaks, accumulation of genomic damage, and cancer predisposition<ref name=":16">Shiloh, Y., Ziv, Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. ''Nat Rev Mol Cell Biol'' '''14''', 197–210 (2013). <nowiki>https://doi.org/10.1038/nrm3546</nowiki></ref> | ||
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|CHEK2; Inactivating mutations | |CHEK2; Inactivating mutations | ||
|Cell-cycle checkpoint control and DNA damage response | |Cell-cycle checkpoint control and DNA damage response | ||
|Failure of G1/S and G2/M checkpoint arrest following DNA damage, allowing propagation of genomic instability | |Failure of G1/S and G2/M checkpoint arrest following DNA damage, allowing propagation of genomic instability<ref name=":16" /> | ||
|- | |- | ||
|TP53; Inactivating or dominant-negative mutations | |TP53; Inactivating or dominant-negative mutations | ||
|Cell-cycle regulation, apoptosis, genome integrity | |Cell-cycle regulation, apoptosis, genome integrity | ||
|Loss of DNA damage–induced cell-cycle arrest and apoptosis, enabling survival and expansion of genetically unstable cells | |Loss of DNA damage–induced cell-cycle arrest and apoptosis, enabling survival and expansion of genetically unstable cells<ref name=":5" /><ref name=":16" /> | ||
|- | |- | ||
|RAD51C / RAD51D; Inactivating mutations | |RAD51C / RAD51D; Inactivating mutations | ||
|Homologous recombination DNA repair | |Homologous recombination DNA repair | ||
|mpaired strand invasion and repair of DNA double-strand breaks, contributing to HRD and hereditary cancer susceptibility | |mpaired strand invasion and repair of DNA double-strand breaks, contributing to HRD and hereditary cancer susceptibility<ref name=":0" /><ref name=":17">Loveday, C., Turnbull, C., Ramsay, E. et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43, 879–882 (2011). <nowiki>https://doi.org/10.1038/ng.893</nowiki></ref> | ||
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==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
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<ref name=":15" />Tischkowitz M, Xia B. PALB2/FANCN: recombining cancer and Fanconi anemia. Cancer Res. 2010 Oct 1;70(19):7353-9. doi: 10.1158/0008-5472.CAN-10-1012. Epub 2010 Sep 21. PMID: 20858716; PMCID: PMC2948578. | <ref name=":15" />Tischkowitz M, Xia B. PALB2/FANCN: recombining cancer and Fanconi anemia. Cancer Res. 2010 Oct 1;70(19):7353-9. doi: 10.1158/0008-5472.CAN-10-1012. Epub 2010 Sep 21. PMID: 20858716; PMCID: PMC2948578. | ||
<ref name=":16" />Shiloh, Y., Ziv, Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol 14, 197–210 (2013). <nowiki>https://doi.org/10.1038/nrm3546</nowiki> | |||
<ref name=":17" />Loveday, C., Turnbull, C., Ramsay, E. et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43, 879–882 (2011). <nowiki>https://doi.org/10.1038/ng.893</nowiki> | |||
==Notes== | ==Notes== | ||