Germline and Somatic Alterations Are Linked to Increased HER2 Expression in Breast Cancer.

germline mutation predisposes to breast cancer. mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neurofibromatosis type 1 (NF1), 9 samples (NF + BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of were identified in two samples and were in three. No mutation was detected in , and HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN gain/amplification of was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in -mutated/deleted samples in comparison with -unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring mutation and CN gain/amplification. gene loss of heterozygosity was observed in 4 of 9 NF + BrCa samples. appeared to have more CN gain in NF + BrCa and exhibited increased mRNA expression in TCGA -altered samples. .