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Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Jan 08; Vol. 23 (2). Date of Electronic Publication: 2022 Jan 08. - Publication Year :
- 2022
-
Abstract
- 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.
- Subjects :
- Alternative Splicing genetics
Alu Elements genetics
Base Sequence
DNA, Neoplasm genetics
Frameshift Mutation genetics
Humans
Male
Middle Aged
Breast Neoplasms, Male genetics
Exons genetics
Fanconi Anemia Complementation Group N Protein genetics
Gene Duplication
Genetic Predisposition to Disease
Neoplasms, Multiple Primary genetics
Prostatic Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Report
- Accession number :
- 35054852
- Full Text :
- https://doi.org/10.3390/ijms23020667