GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2): Difference between revisions
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|BRCA1; Loss-of-function germline or somatic mutations | |BRCA1; Loss-of-function germline or somatic mutations | ||
|Homologous recombination (HR) DNA double-strand break repair; DNA damage response | |Homologous recombination (HR) DNA double-strand break repair; DNA damage response | ||
|Defective DNA repair leading to genomic instability and chromosomal aberrations; increased cancer susceptibility. Tumors demonstrate homologous recombination deficiency (HRD) and sensitivity to platinum agents and PARP inhibitors | |Defective DNA repair leading to genomic instability and chromosomal aberrations; increased cancer susceptibility. Tumors demonstrate homologous recombination deficiency (HRD) and sensitivity to platinum agents and PARP inhibitors<ref name=":0" /><ref name=":5" /><ref name=":10" /> | ||
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|BRCA2; Loss-of-function germline or somatic mutations | |BRCA2; Loss-of-function germline or somatic mutations | ||
|Homologous recombination DNA repair (RAD51 loading and stabilization) | |Homologous recombination DNA repair (RAD51 loading and stabilization) | ||
|Impaired repair of DNA double-strand breaks, genomic instability, and tumorigenesis; HRD phenotype with therapeutic vulnerability to PARP inhibition | |Impaired repair of DNA double-strand breaks, genomic instability, and tumorigenesis; HRD phenotype with therapeutic vulnerability to PARP inhibition<ref name=":0" /><ref name=":5" /><ref name=":10" /> | ||
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|PALB2; Inactivating mutations | |PALB2; Inactivating mutations | ||
|BRCA1–BRCA2–PALB2 DNA repair complex (HR pathway) | |BRCA1–BRCA2–PALB2 DNA repair complex (HR pathway) | ||
|Disruption of BRCA1–BRCA2 interaction, defective homologous recombination, and increased cancer risk similar to BRCA2-associated tumors | |Disruption of BRCA1–BRCA2 interaction, defective homologous recombination, and increased cancer risk similar to BRCA2-associated tumors<ref name=":0" /><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> | ||
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|ATM; Inactivating mutations | |ATM; Inactivating mutations | ||
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<ref name=":14" />Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, Boyd J, Reis-Filho JS, Ashworth A. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008 Feb 28;451(7182):1111-5. doi: 10.1038/nature06548. Epub 2008 Feb 10. PMID: 18264088. | <ref name=":14" />Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, Boyd J, Reis-Filho JS, Ashworth A. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008 Feb 28;451(7182):1111-5. doi: 10.1038/nature06548. Epub 2008 Feb 10. PMID: 18264088. | ||
<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. | |||
==Notes== | ==Notes== | ||