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Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers
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 variant...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563793/ https://www.ncbi.nlm.nih.gov/pubmed/32957588 http://dx.doi.org/10.3390/jcm9093003 |
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author | 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 Falchetto Pellegrini, Patrizia Speranza, Annarita Stanzani, Gianluca Vitale, Valeria Pizzuti, Antonio Torrisi, Maria Rosaria Piane, Maria |
author_facet | 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 Falchetto Pellegrini, Patrizia Speranza, Annarita Stanzani, Gianluca Vitale, Valeria Pizzuti, Antonio Torrisi, Maria Rosaria Piane, Maria |
author_sort | Germani, Aldo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7563793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75637932020-10-27 Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers 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 Falchetto Pellegrini, Patrizia Speranza, Annarita Stanzani, Gianluca Vitale, Valeria Pizzuti, Antonio Torrisi, Maria Rosaria Piane, Maria J Clin Med Article 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. MDPI 2020-09-17 /pmc/articles/PMC7563793/ /pubmed/32957588 http://dx.doi.org/10.3390/jcm9093003 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Falchetto Pellegrini, Patrizia Speranza, Annarita Stanzani, Gianluca Vitale, Valeria Pizzuti, Antonio Torrisi, Maria Rosaria Piane, Maria Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title | Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title_full | Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title_fullStr | Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title_full_unstemmed | Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title_short | Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers |
title_sort | beyond brca1 and brca2: deleterious variants in dna repair pathway genes in italian families with breast/ovarian and pancreatic cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563793/ https://www.ncbi.nlm.nih.gov/pubmed/32957588 http://dx.doi.org/10.3390/jcm9093003 |
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