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Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer

PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast canc...

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Autores principales: Bouras, Ahmed, Lafaye, Cyril, Leone, Melanie, Kherraf, Zine-Eddine, Martin-Denavit, Tanguy, Fert-Ferrer, Sandra, Calender, Alain, Boutry-Kryza, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775416/
https://www.ncbi.nlm.nih.gov/pubmed/35054852
http://dx.doi.org/10.3390/ijms23020667
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author Bouras, Ahmed
Lafaye, Cyril
Leone, Melanie
Kherraf, Zine-Eddine
Martin-Denavit, Tanguy
Fert-Ferrer, Sandra
Calender, Alain
Boutry-Kryza, Nadia
author_facet Bouras, Ahmed
Lafaye, Cyril
Leone, Melanie
Kherraf, Zine-Eddine
Martin-Denavit, Tanguy
Fert-Ferrer, Sandra
Calender, Alain
Boutry-Kryza, Nadia
author_sort Bouras, Ahmed
collection PubMed
description PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in PALB2, implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of PALB2 variants and may improve the yield of genetic diagnoses in this field.
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spelling pubmed-87754162022-01-21 Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer Bouras, Ahmed Lafaye, Cyril Leone, Melanie Kherraf, Zine-Eddine Martin-Denavit, Tanguy Fert-Ferrer, Sandra Calender, Alain Boutry-Kryza, Nadia Int J Mol Sci Case Report PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in PALB2, implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of PALB2 variants and may improve the yield of genetic diagnoses in this field. MDPI 2022-01-08 /pmc/articles/PMC8775416/ /pubmed/35054852 http://dx.doi.org/10.3390/ijms23020667 Text en © 2022 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 Case Report
Bouras, Ahmed
Lafaye, Cyril
Leone, Melanie
Kherraf, Zine-Eddine
Martin-Denavit, Tanguy
Fert-Ferrer, Sandra
Calender, Alain
Boutry-Kryza, Nadia
Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title_full Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title_fullStr Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title_full_unstemmed Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title_short Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
title_sort identification and characterization of an exonic duplication in palb2 in a man with synchronous breast and prostate cancer
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775416/
https://www.ncbi.nlm.nih.gov/pubmed/35054852
http://dx.doi.org/10.3390/ijms23020667
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