Characterizing <i>PALB2</i> intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing

<h4>Introduction</h4>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 <i>PALB2</i> to determine its pathogenicity significance.<h4>Methods</h4>A 52-year-old female with triple-negative breast cancer was diagnosed with a novel <i>PALB2</i> LGR. An efficient and accurate methodology was applied, combining long-read sequencing and transcript analysis for the rapid characterization of the duplication.<h4>Results</h4>Duplication of exons 5 and 6 of <i>PALB2</i> was validated by transcript analysis. Long-read sequencing enabled the localization of breakpoints within <i>Alu</i> elements, providing insights into the mechanism of duplication via non-allelic homologous recombination.<h4>Conclusion</h4>Using our combined methodology, we reclassified the <i>PALB2</i> duplication as a pathogenic variant. This reclassification suggests a possible causative link between this specific genetic alteration and the aggressive phenotype of the patient.