Multi-omics profiling of younger Asian breast cancers reveals distinctive molecular signatures

• DOI: 10.1038/s41467-018-04129-4
• Publication Date: 2018-04-24T11:31:02Z
• Authors: Zhengyan Kan; Ying Ding; Jinho Kim; Hae Hyun Jung; Woosung Chung; Samir Lal; Soonweng Cho; Julio Fernandez-B...; Se Kyung Lee; Seok Won Kim; Jeong Eon Lee; Yoon-La Choi; Shibing Deng; Ji-Yeon Kim; Jin Seok Ahn; Ying Sha; Xinmeng Jasmine Mu; Jae-Yong Nam; Young-Hyuck Im; Soohyeon Lee; Woong-Yang Park; Seok Jin Nam; Yeon Hee Park
• Keywords: Adult; Receptor, ErbB-2; Science; Breast Neoplasms; Article; Cohort Studies; 03 medical and health sciences; Asian People; Transforming Growth Factor beta; Biomarkers, Tumor; Tumor Microenvironment; Humans; Neoplasm Staging; BRCA2 Protein; 0303 health sciences; BRCA1 Protein; Q; Estrogen Receptor alpha; Middle Aged; 3. Good health; Carcinoma, Ductal; Postmenopause; Carcinoma, Lobular; Premenopause; Female; Transcriptome

AbstractBreast 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.