Prediction of Specific Survival and Clinicopathological Impact of Somatic PALB2 Mutations and Pathogenic/Likely Pathogenic Variants (PV/LPV) in Breast Cancer: A Cohort Study of 81 Patients

Abstract

PALB2 plays a crucial role in DNA repair by interacting with BRCA1 and BRCA2. To clarify the clinicopathological impact of somatic PALB2 variants, we analyzed tumor DNA extracted from formalin-fixed, paraffin-embedded (FFPE) breast cancer specimens from 81 patients. Targeted next-generation sequencing identified 1 514 variants, including 84 pathogenic or likely pathogenic variants and 9 genes with high mutation frequency; 2 deleterious somatic PALB2 variants were detected in 33% of samples. To explore transcriptional effects, we analyzed publicly available METABRIC mRNA expression data and found that elevated PALB2 mRNA levels were significantly associated with ER-/PR- tumors and poorer survival outcomes. High PALB2 expression remained an independent predictor of shorter overall survival and relapse-free survival. These findings highlight the clinical importance of somatic PALB2 mutations and the prognostic value of PALB2 expression in breast cancer.