Alu–Mediated Duplication and Deletion of Exon 11 Are Frequent Mechanisms of PALB2 Inactivation, Predisposing Individuals to Hereditary Breast–Ovarian Cancer Syndrome

Large genomic rearrangements of the PALB2 gene, especially deletions and duplications, are associated with hereditary breast–ovarian cancer. This study investigates intronic breakpoints linked to rearrangements in PALB2 exon 11, which is crucial for understanding the mechanisms affecting patients with hereditary breast and ovarian syndrome. Through next-generation sequencing, one duplication and three deletions were identified, confirmed by Multiplex Ligation-Dependent Probe Amplification. Detailed characterization revealed a tandem duplication of 5134 base pairs mediated by AluY repeats and identical deletions in three unrelated patients promoted by AluSx elements, resulting in a truncated PALB2 protein. These findings highlight the instability of intronic regions flanking exon 11 and suggest directions for future research on the prevalence and functional implications of these genomic alterations.