Sun Woo Young, Lee Jina, Kim Bong Kyun, Kim Jong Ok, Park Joonhong
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Diagnostics (Basel). 2021 Mar 1;11(3):416. doi: 10.3390/diagnostics11030416.
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.
本研究旨在阐明韩国三阴性乳腺癌（TNBC）与其他乳腺癌（BC）亚型之间的基因差异。TNBC定义为无激素受体且人表皮生长因子受体2（HER2）无扩增。采用Ion Torrent Oncomine Comprehensive Assay（OCA）v3的DNA检测板对48个样本进行体细胞改变鉴定。在总共102个改变（37个无义突变、35个错义突变、8个移码突变和22个扩增）中，新发现了30个核苷酸改变（24个无义突变、1个错义突变和5个移码突变）。八个最常发生改变的基因是 、 、 、 、 、 、 和 。TNBC在 中的突变频率显著较低（TNBC与激素受体阳性且HER2阴性乳腺癌[HRPBC]相比， = 0.009），但在 中的突变频率较高（TNBC与HRPBC相比， = 0.036；TNBC与激素受体阳性且HER2阳性乳腺癌[HHPBC]相比， = 0.004）。由于HRPBC（ < 0.001），TNBC的Ki-67表达通常比任何阳性BC都高（ = 0.004）。与其他亚型（63.7 ± 11.0岁）相比，Ki-67高表达/未突变 /突变 的TNBC发病年龄较轻（52.2 ± 7.6岁）。Ki-67高表达/未突变 /突变 的TNBC可能与相对早期发病的乳腺癌有关。这些发现证明了TNBC与其他BC亚型之间的基因组异质性，并可能为TNBC患者的分子靶向治疗提供一种新方法。
