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

Zhengyan Kan (), Ying Ding, Jinho Kim, Hae Hyun Jung, Woosung Chung, Samir Lal, Soonweng Cho, Julio Fernandez-Banet, 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 () and Yeon Hee Park ()
Additional contact information
Zhengyan Kan: Pfizer Oncology Research
Ying Ding: Pfizer Oncology Research
Jinho Kim: Sungkyunkwan University School of Medicine
Hae Hyun Jung: Sungkyunkwan University School of Medicine
Woosung Chung: Sungkyunkwan University School of Medicine
Samir Lal: Pfizer Oncology Research
Soonweng Cho: Pfizer Oncology Research
Julio Fernandez-Banet: Pfizer Oncology Research
Se Kyung Lee: Sungkyunkwan University School of Medicine
Seok Won Kim: Sungkyunkwan University School of Medicine
Jeong Eon Lee: Sungkyunkwan University School of Medicine
Yoon-La Choi: Sungkyunkwan University School of Medicine
Shibing Deng: Pfizer Oncology Research
Ji-Yeon Kim: Sungkyunkwan University School of Medicine
Jin Seok Ahn: Sungkyunkwan University School of Medicine
Ying Sha: Pfizer Oncology Research
Xinmeng Jasmine Mu: Pfizer Oncology Research
Jae-Yong Nam: Sungkyunkwan University School of Medicine
Young-Hyuck Im: Sungkyunkwan University School of Medicine
Soohyeon Lee: Pfizer Oncology
Woong-Yang Park: Sungkyunkwan University School of Medicine
Seok Jin Nam: Sungkyunkwan University School of Medicine
Yeon Hee Park: Sungkyunkwan University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-04129-4

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