The Transcriptomic Profile Underlying Somatic Monoallelic BRCA1 Inactivation: A Biomarker for Breast Cancer Prognosis

Background and Objectives: Most of the research on the role of the BRCA1 gene in breast cancer is focused on monoallelic germline alterations and loss of heterozygosity in tumors. The aim of this study was to identify the characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its correlation with event-free breast cancer survival.
Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signaling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed.
Results: Kaplan-Meier analysis showed a tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation to be a favorable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusions: In this study, we identified transcriptomic profiles of differentially expressed genes TPSD1, FABP4, CARTPT, and MMP9 as indicative of homologous recombination-impaired tumors with a tendency for better therapy results.