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Open AccessArticle

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers

1
Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, 00100 Rome, Italy
2
Sant’Andrea University Hospital, 00100 Rome, Italy
3
Department of Radiological Anatomopathological, Oncological Science, “Sapienza” University of Rome, 00100 Rome, Italy
4
Umberto I University Hospital, 00100 Rome, Italy
5
Department of Medical and Surgical Sciences and Translational Medicine, “Sapienza” University of Rome, 00100 Rome, Italy
6
Unit of Radiation Oncology, Sant’Andrea Hospital, Sapienza University of Rome, 00100 Rome, Italy
7
Department of Molecular Medicine, “Sapienza” University of Rome, 00100 Roma, Italy
8
Department of Experimental Medicine, “Sapienza” University of Rome, 00100 Rome, Italy
9
Clinical Genomics Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally.
J. Clin. Med. 2020, 9(9), 3003; https://doi.org/10.3390/jcm9093003
Received: 11 August 2020 / Revised: 4 September 2020 / Accepted: 10 September 2020 / Published: 17 September 2020
(This article belongs to the Section Oncology)
The 5–10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10–20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches. View Full-Text
Keywords: hereditary breast/ovarian cancer; pancreatic cancer; next-generation sequencing; gene panel; DNA repair genes hereditary breast/ovarian cancer; pancreatic cancer; next-generation sequencing; gene panel; DNA repair genes
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MDPI and ACS Style

Germani, A.; Petrucci, S.; De Marchis, L.; Libi, F.; Savio, C.; Amanti, C.; Bonifacino, A.; Campanella, B.; Capalbo, C.; Lombardi, A.; Maggi, S.; Mattei, M.; Osti, M.F.; Pellegrini, P.; Speranza, A.; Stanzani, G.; Vitale, V.; Pizzuti, A.; Torrisi, M.R.; Piane, M. Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers. J. Clin. Med. 2020, 9, 3003. https://doi.org/10.3390/jcm9093003

AMA Style

Germani A, Petrucci S, De Marchis L, Libi F, Savio C, Amanti C, Bonifacino A, Campanella B, Capalbo C, Lombardi A, Maggi S, Mattei M, Osti MF, Pellegrini P, Speranza A, Stanzani G, Vitale V, Pizzuti A, Torrisi MR, Piane M. Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers. Journal of Clinical Medicine. 2020; 9(9):3003. https://doi.org/10.3390/jcm9093003

Chicago/Turabian Style

Germani, Aldo; Petrucci, Simona; De Marchis, Laura; Libi, Fabio; Savio, Camilla; Amanti, Claudio; Bonifacino, Adriana; Campanella, Barbara; Capalbo, Carlo; Lombardi, Augusto; Maggi, Stefano; Mattei, Mauro; Osti, Mattia F.; Pellegrini, Patrizia; Speranza, Annarita; Stanzani, Gianluca; Vitale, Valeria; Pizzuti, Antonio; Torrisi, Maria R.; Piane, Maria. 2020. "Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers" J. Clin. Med. 9, no. 9: 3003. https://doi.org/10.3390/jcm9093003

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