AUTHOR=Ban Iulian O. , Chabert Alice , Guignard Thomas , Puechberty Jacques , Cabello-Aguilar Simon , Pujol Pascal , Vendrell Julie A. , Solassol Jérôme 

TITLE=Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1355715

DOI=10.3389/fonc.2024.1355715

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Accurate identification and characterization of Large Genomic Rearrangements (LGR), especially duplications, are crucial for precise diagnosis and risk assessment. In this report, we characterized an intragenic duplication breakpoint of <italic>PALB2</italic> to determine its pathogenicity significance.</p></sec><sec><title>Methods</title><p>A 52-year-old female with triple-negative breast cancer was diagnosed with a novel <italic>PALB2</italic> LGR. An efficient and accurate methodology was applied, combining long-read sequencing and transcript analysis for the rapid characterization of the duplication.</p></sec><sec><title>Results</title><p>Duplication of exons 5 and 6 of <italic>PALB2</italic> was validated by transcript analysis. Long-read sequencing enabled the localization of breakpoints within <italic>Alu</italic> elements, providing insights into the mechanism of duplication via non-allelic homologous recombination.</p></sec><sec><title>Conclusion</title><p>Using our combined methodology, we reclassified the <italic>PALB2</italic> duplication as a pathogenic variant. This reclassification suggests a possible causative link between this specific genetic alteration and the aggressive phenotype of the patient.</p></sec>