Journal Article

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

Sha, Ying, Mu, Xinmeng Jasmine, Jung, Hae Hyun, Ding, Ying, Kim, Seok Won, Nam, Jae-Yong, Im, Young-Hyuck, Park, Yeon Hee, Park, Woong-Yang, Kan, Zhengyan, Fernandez-Banet, Julio, Lee, Jeong Eon, Choi, Yoon-La, Cho, Soonweng, Kim, Ji-Yeon, Kim, Jinho, Lee, Soohyeon, Deng, Shibing, Nam, Seok Jin, Lal, Samir, Ahn, Jin Seok, Lee, Se Kyung, Chung, Woosung

2018

Overview

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. While breast cancer incidence in the Asia Pacific region is rising, the molecular basis remains poorly characterized. Here the authors perform genomic screening of 187 Korean breast cancer patients and find differences in molecular subtype distribution, mutation pattern and prevalence, and gene expression signature when compared to TCGA.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/39 / 45/23 / 45/91 / 631/114/2164 / 631/67/1347 / 631/67/69 / Adult / Age groups / Asian Continental Ancestry Group / Biomarkers, Tumor - genetics / Biomarkers, Tumor - immunology / BRCA1 protein / BRCA1 Protein - genetics / BRCA1 Protein - immunology / BRCA2 protein / BRCA2 Protein - genetics / BRCA2 Protein - immunology / Breast cancer / Breast Neoplasms - ethnology / Breast Neoplasms - genetics / Breast Neoplasms - immunology / Breast Neoplasms - pathology / Carcinoma, Ductal - ethnology / Carcinoma, Ductal - genetics / Carcinoma, Ductal - immunology / Carcinoma, Ductal - pathology / Carcinoma, Lobular - ethnology / Carcinoma, Lobular - genetics / Carcinoma, Lobular - immunology / Carcinoma, Lobular - pathology / Cohort Studies / Enrichment / ErbB-2 protein / ESR1 protein / Estrogen Receptor alpha - genetics / Estrogen Receptor alpha - immunology / Estrogens / European Continental Ancestry Group / Female / Gene expression / Genomes / Genomics / Homologous recombination / Homologous recombination repair / Homology / Humanities and Social Sciences / Humans / Medicine / Middle Aged / Molecular chains / Mortality / multidisciplinary / Mutation / Neoplasm Staging / Oncology / p53 Protein / Patients / Postmenopause / Premenopause / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - immunology / Science / Science (multidisciplinary) / Signatures / Transcriptome / Transforming Growth Factor beta - genetics / Transforming Growth Factor beta - immunology / Tumor Microenvironment - genetics / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - immunology / Tumors / Whole Exome Sequencing