Pfizer Oncology Research, San Diego, CA, 92121, USA.
Samsung Genome Institute, Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Nat Commun. 2018 Apr 30;9(1):1725. doi: 10.1038/s41467-018-04129-4.
Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA. We also observe increased mutation prevalence affecting BRCA1, BRCA2, and TP53 in SMC with an enrichment of a mutation signature linked to homologous recombination repair deficiency in TNBC. Finally, virtual microdissection and multivariate analyses reveal that Korean BC status is independently associated with increased TIL and decreased TGF-β signaling expression signatures, suggesting that younger Asian BCs harbor more immune-active microenvironment than western BCs.
亚太地区的乳腺癌(BC)患者以年轻患者居多,发病率迅速上升,但其分子基础仍知之甚少。在这里,我们分析了来自韩国 BC 队列(SMC)的 187 个原发性肿瘤的外显子组和转录组,该队列中绝经前患者较多,并与主要为高加索人和绝经后 BC 队列(TCGA)进行了系统比较。SMC 中 HER2+和 Luminal B 亚型的比例较高,Luminal A 亚型的比例较低,与 TCGA 相比,ESR1 表达降低。我们还观察到在 SMC 中,BRCA1、BRCA2 和 TP53 的突变发生率增加,与三阴性乳腺癌中同源重组修复缺陷相关的突变特征富集。最后,虚拟微观解剖和多变量分析表明,韩国 BC 状态与增加的 TIL 和减少的 TGF-β信号表达特征独立相关,这表明年轻的亚洲 BC 比西方 BC 具有更活跃的免疫微环境。
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