Table_3_Whole Exome Sequencing in BRCA1-2 Candidate Families: The Contribution of Other Cancer Susceptibility Genes.docx
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is a condition in which the risk of breast and ovarian cancer is higher than in the general population. The prevalent pathogenesis is attributable to inactivating variants of the BRCA1-2 highly penetrant genes, however, other cancer susceptibility genes may also be involved. By Whole Exome Sequencing (WES) we analyzed a series of 200 individuals selected for genetic testing in BRCA1-2 genes according to the updated National Comprehensive Cancer Network (NCCN) guidelines. Analysis by MLPA was performed to detect large BRCA1-2 deletions/duplications. Focusing on BRCA1-2 genes, data analysis identified 11 cases with pathogenic variants (4 in BRCA1 and 7 in BRCA1-2) and 12 with uncertain variants (7 in BRCA1 and 5 in BRCA2). Only one case was found with a large BRCA1 deletion. Whole exome analysis allowed to characterize pathogenic variants in 21 additional genes: 10 genes more traditionally associated to breast and ovarian cancer (ATM, BRIP1, CDH1, PALB2, PTEN, RAD51C, and TP53) (5% diagnostic yield) and 11 in candidate cancer susceptibility genes (DPYD, ERBB3, ERCC2, MUTYH, NQO2, NTHL1, PARK2, RAD54L, and RNASEL). In conclusion, this study allowed a personalized risk assessment and clinical surveillance in an increased number of HBOC families and to broaden the spectrum of causative variants also to candidate “non-canonical” genes.
History
References
- https://doi.org//10.1002/ijc.25516
- https://doi.org//10.3322/caac.21332
- https://doi.org//10.1007/s10689-011-9506-2
- https://doi.org//10.1136/jmg.2004.028829
- https://doi.org//10.1073/pnas.85.9.3044
- https://doi.org//10.1126/science.2270482
- https://doi.org//10.1126/science.7545954
- https://doi.org//10.1200/JCO.2006.09.1066
- https://doi.org//10.1001/jama.2017.7112
- https://doi.org//10.1001/jama.2010.1237
- https://doi.org//10.3322/canjclin.57.2.75
- https://doi.org//10.1126/science.aam7344
- https://doi.org//10.1002/cncr.30498
- https://doi.org//10.1007/s10689-016-9956-7
- https://doi.org//10.18632/oncotarget.16791
- https://doi.org//10.1007/s10549-016-3948-z
- https://doi.org//10.1038/gim.2014.40
- https://doi.org//10.1200/JCO.2015.65.0747
- https://doi.org//10.3390/cancers12092415
- https://doi.org//10.1038/gim.2015.166
- https://doi.org//10.1038/nrc.2016.72
- https://doi.org//10.3389/fgene.2019.01005
- https://doi.org//10.6004/jnccn.2020.0017
- https://doi.org//10.1093/bioinformatics/btp698
- https://doi.org//10.1101/201178
- https://doi.org//10.1007/s13167-010-0037-y
- https://doi.org//10.1016/j.jmoldx.2018.06.003
- https://doi.org//10.1001/jamanetworkopen.2018.2140
- https://doi.org//10.1002/humu.23842
- https://doi.org//10.1042/BSR20182471
- https://doi.org//10.1002/humu.23818
- https://doi.org//10.1038/s41598-018-27315-2
- https://doi.org//10.1002/cam4.2093
- https://doi.org//10.1002/j.1460-2075.1995.tb00301.x
- https://doi.org//10.1038/s10038-019-0612-6
- https://doi.org//10.1200/JCO.2013.53.6656
- https://doi.org//10.1046/j.1365-2133.2003.05322.x
- https://doi.org//10.1200/JCO.2015.61.2408
- https://doi.org//10.3390/cancers12030637
- https://doi.org//10.1002/humu.23673
- https://doi.org//10.1007/s10549-019-05144-9
- https://doi.org//10.1002/humu.20768
- https://doi.org//10.3389/fonc.2018.00583
- https://doi.org//10.1002/ijc.27761
- https://doi.org//10.1038/s41598-019-45281-1
- https://doi.org//10.1086/340450
- https://doi.org//10.1136/jmg.37.11.828
- https://doi.org//10.1056/nejmoa1400382
- https://doi.org//10.1002/gepi.21971
- https://doi.org//10.1038/ng1902
- https://doi.org//10.1016/S0092-8674%2801%2900304-X
- https://doi.org//10.1016/j.cell.2015.09.033
- https://doi.org//10.1200/JCO.2015.64.0334
- https://doi.org//10.1007/s10549-010-1095-5
- https://doi.org//10.1186/bcr2619
- https://doi.org//10.1007/s10549-011-1677-x
- https://doi.org//10.3389/fonc.2012.00083
- https://doi.org//10.22037/ghfbb.v6i0.458
- https://doi.org//10.1002/ijc.30197
- https://doi.org//10.1016/j.ejca.2003.12.004
- https://doi.org//10.1038/s41598-020-62662-z
- https://doi.org//10.1172/JCI118830
- https://doi.org//10.1038/cgt.2008.15
- https://doi.org//10.1038/s41388-019-1001-5
- https://doi.org//10.1038/leu.2016.173
- https://doi.org//10.1371/journal.pgen.1006248
- https://doi.org//10.1006/abbi.1997.0344
- https://doi.org//10.1093/hmg/ddp171
- https://doi.org//10.1128/mcb.22.17.6111-6121.2002
- https://doi.org//10.1016/j.ccell.2018.12.011
- https://doi.org//10.1038/33416
- https://doi.org//10.1158/1078-0432.CCR-03-0086
- https://doi.org//10.1038/ng.491
- https://doi.org//10.1073/pnas.0931262100
- https://doi.org//10.1038/sj.onc.1202692
- https://doi.org//10.1002/j.1460-2075.1993.tb05999.x
- https://doi.org//10.1089/107999000750053762