By analyzing multiple gene panels, next-generation sequencing is more effective than conventional procedures in identifying disease-related mutations that are useful for clinical decision-making. Here, we aimed to test the efficacy of an 84 genes customized-panel in BRCA1 and BRCA2 mutation-negative patients. Twenty-four patients were enrolled in this study. DNA libraries were prepared using a picodroplet PCR-based approach and sequenced with the MiSeq System. Highly putative pathogenic mutations were identified in genes other than the commonly tested BRCA1/2: 2 pathogenic mutations one in TP53 and one in MUTYH; 2 missense variants in MSH6 and ATM, respectively; 2 frameshift variants in KLLN, and ATAD2, respectively; an intronic variant in ANPEP, and 3 not functionally known variants (a frameshift variant in ATM a nonsense variant in ATM and a missense variant in NFE2L2). Our results show that this molecular screening will increase diagnostic sensitivity leading to a better risk assessment in breast cancer patients and their families. This strategy could also reveal genes that have a higher penetrance for breast and ovarian cancers by matching gene mutation with familial and clinical data, thereby increasing information about hereditary breast and ovarian cancer genetics and improving cancer prevention measures or therapeutic approaches. (C) 2018 Published by Elsevier B.V.

A multi-gene panel beyond BRCA1/BRCA2 to identify new breast cancer-predisposing mutations by a picodroplet PCR followed by a next-generation sequencing strategy: a pilot study

D'Argenio, Valeria
2019-01-01

Abstract

By analyzing multiple gene panels, next-generation sequencing is more effective than conventional procedures in identifying disease-related mutations that are useful for clinical decision-making. Here, we aimed to test the efficacy of an 84 genes customized-panel in BRCA1 and BRCA2 mutation-negative patients. Twenty-four patients were enrolled in this study. DNA libraries were prepared using a picodroplet PCR-based approach and sequenced with the MiSeq System. Highly putative pathogenic mutations were identified in genes other than the commonly tested BRCA1/2: 2 pathogenic mutations one in TP53 and one in MUTYH; 2 missense variants in MSH6 and ATM, respectively; 2 frameshift variants in KLLN, and ATAD2, respectively; an intronic variant in ANPEP, and 3 not functionally known variants (a frameshift variant in ATM a nonsense variant in ATM and a missense variant in NFE2L2). Our results show that this molecular screening will increase diagnostic sensitivity leading to a better risk assessment in breast cancer patients and their families. This strategy could also reveal genes that have a higher penetrance for breast and ovarian cancers by matching gene mutation with familial and clinical data, thereby increasing information about hereditary breast and ovarian cancer genetics and improving cancer prevention measures or therapeutic approaches. (C) 2018 Published by Elsevier B.V.
2019
Cancer risk
Gene panel testing
Germinal predisposing mutations
Hereditary breast and ovarian cancer
Next-generation sequencing
Picodroplet PCR
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12078/13458
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