Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression.

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were , , , , , , , and . TNBC had significantly lower mutation frequency in (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], = 0.009), but higher mutation frequency in (TNBC vs. HRPBC, = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC ( = 0.004) due to HRPBC ( < 0.001). TNBC with high Ki-67/unmutated /mutated appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated /mutated may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.