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Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer

Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes BRCA1 and BRCA2, many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel...

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Autores principales: Turchiano, Antonella, Piglionica, Marilidia, Martino, Stefania, Bagnulo, Rosanna, Garganese, Antonella, De Luisi, Annunziata, Chirulli, Stefania, Iacoviello, Matteo, Stasi, Michele, Tabaku, Ornella, Meneleo, Eleonora, Capurso, Martina, Crocetta, Silvia, Lattarulo, Simone, Krylovska, Yevheniia, Lastella, Patrizia, Forleo, Cinzia, Stella, Alessandro, Bukvic, Nenad, Simone, Cristiano, Resta, Nicoletta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454640/
https://www.ncbi.nlm.nih.gov/pubmed/37628581
http://dx.doi.org/10.3390/genes14081530
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author Turchiano, Antonella
Piglionica, Marilidia
Martino, Stefania
Bagnulo, Rosanna
Garganese, Antonella
De Luisi, Annunziata
Chirulli, Stefania
Iacoviello, Matteo
Stasi, Michele
Tabaku, Ornella
Meneleo, Eleonora
Capurso, Martina
Crocetta, Silvia
Lattarulo, Simone
Krylovska, Yevheniia
Lastella, Patrizia
Forleo, Cinzia
Stella, Alessandro
Bukvic, Nenad
Simone, Cristiano
Resta, Nicoletta
author_facet Turchiano, Antonella
Piglionica, Marilidia
Martino, Stefania
Bagnulo, Rosanna
Garganese, Antonella
De Luisi, Annunziata
Chirulli, Stefania
Iacoviello, Matteo
Stasi, Michele
Tabaku, Ornella
Meneleo, Eleonora
Capurso, Martina
Crocetta, Silvia
Lattarulo, Simone
Krylovska, Yevheniia
Lastella, Patrizia
Forleo, Cinzia
Stella, Alessandro
Bukvic, Nenad
Simone, Cristiano
Resta, Nicoletta
author_sort Turchiano, Antonella
collection PubMed
description Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes BRCA1 and BRCA2, many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel testing have allowed the simultaneous sequencing of BRCA1/2 with these genes in a cost-effective way. Germline DNA from 521 cases with BC fulfilling diagnostic criteria for hereditary BC were screened with multigene NGS testing. Pathogenic (PVs) and likely pathogenic (LPVs) variants in moderate penetrance genes were identified in 15 out of 521 patients (2.9%), including 2 missense, 7 non-sense, 1 indel, and 3 splice variants, as well as two different exon deletions, as follows: ATM (n = 4), CHEK2 (n = 5), PALB2 (n = 2), RAD51C (n = 1), and RAD51D (n = 3). Moreover, the segregation analysis of PVs and LPVs into first-degree relatives allowed the detection of CHEK2 variant carriers diagnosed with in situ melanoma and clear cell renal cell carcinoma (ccRCC), respectively. Extended testing beyond BRCA1/2 identified PVs and LPVs in a further 2.9% of BC patients. In conclusion, panel testing yields more accurate genetic information for appropriate counselling, risk management, and preventive options than assessing BRCA1/2 alone.
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spelling pubmed-104546402023-08-26 Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer Turchiano, Antonella Piglionica, Marilidia Martino, Stefania Bagnulo, Rosanna Garganese, Antonella De Luisi, Annunziata Chirulli, Stefania Iacoviello, Matteo Stasi, Michele Tabaku, Ornella Meneleo, Eleonora Capurso, Martina Crocetta, Silvia Lattarulo, Simone Krylovska, Yevheniia Lastella, Patrizia Forleo, Cinzia Stella, Alessandro Bukvic, Nenad Simone, Cristiano Resta, Nicoletta Genes (Basel) Article Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes BRCA1 and BRCA2, many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel testing have allowed the simultaneous sequencing of BRCA1/2 with these genes in a cost-effective way. Germline DNA from 521 cases with BC fulfilling diagnostic criteria for hereditary BC were screened with multigene NGS testing. Pathogenic (PVs) and likely pathogenic (LPVs) variants in moderate penetrance genes were identified in 15 out of 521 patients (2.9%), including 2 missense, 7 non-sense, 1 indel, and 3 splice variants, as well as two different exon deletions, as follows: ATM (n = 4), CHEK2 (n = 5), PALB2 (n = 2), RAD51C (n = 1), and RAD51D (n = 3). Moreover, the segregation analysis of PVs and LPVs into first-degree relatives allowed the detection of CHEK2 variant carriers diagnosed with in situ melanoma and clear cell renal cell carcinoma (ccRCC), respectively. Extended testing beyond BRCA1/2 identified PVs and LPVs in a further 2.9% of BC patients. In conclusion, panel testing yields more accurate genetic information for appropriate counselling, risk management, and preventive options than assessing BRCA1/2 alone. MDPI 2023-07-26 /pmc/articles/PMC10454640/ /pubmed/37628581 http://dx.doi.org/10.3390/genes14081530 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Turchiano, Antonella
Piglionica, Marilidia
Martino, Stefania
Bagnulo, Rosanna
Garganese, Antonella
De Luisi, Annunziata
Chirulli, Stefania
Iacoviello, Matteo
Stasi, Michele
Tabaku, Ornella
Meneleo, Eleonora
Capurso, Martina
Crocetta, Silvia
Lattarulo, Simone
Krylovska, Yevheniia
Lastella, Patrizia
Forleo, Cinzia
Stella, Alessandro
Bukvic, Nenad
Simone, Cristiano
Resta, Nicoletta
Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title_full Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title_fullStr Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title_full_unstemmed Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title_short Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
title_sort impact of high-to-moderate penetrance genes on genetic testing: looking over breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454640/
https://www.ncbi.nlm.nih.gov/pubmed/37628581
http://dx.doi.org/10.3390/genes14081530
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