Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome

Women with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS) have up to 85% lifetime risk of female breast cancer (BC). We previously showed that PHTS-derived BCs are distinct from sporadic BCs both at the clinical and genomic levels. In this study, we examined somatic copy number variations (CNV) and transcriptome data to further characterize the somatic landscape of PHTS-derived BCs. We analyzed exome sequencing data from 44 BCs from women with PHTS for CNV. The control group comprised of 558 women with sporadic BCs from The Cancer Genome Atlas (TCGA) dataset. Here, we found that PHTS-derived BCs have several distinct CNV peaks compared to TCGA. Furthermore, RNA sequencing data revealed that PHTS-derived BCs have a distinct immunologic cell type signature, which points toward cancer immune evasion. Transcriptomic data also revealed PHTS-derived BCs with pathogenic germline PTEN variants appear to have vitamin E degradation as a key pathway associated with tumorigenesis. In conclusion, our study revealed distinct CNV x transcript features in PHTS-derived BCs, which further facilitate understanding of BC biology arising in the setting of germline PTEN mutations.