Open AccessIntegrative molecular profiling identifies a novel cluster of estrogen receptor‐positive breast cancer in very young women
Author(s) -
Park Charny,
Yoon KyongAh,
Kim Jihyun,
Park In Hae,
Park Soo Jin,
Kim Min Kyeong,
Jang Wooyeong,
Cho Soo Young,
Park Boyoung,
Kong SunYoung,
Lee Eun Sook
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13982
Subject(s) - breast cancer , estrogen receptor , apobec , biology , transcriptome , gene expression profiling , cancer research , copy number variation , estrogen receptor alpha , exome sequencing , gene , cancer , oncology , medicine , genetics , gene expression , mutation , genome
Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor ( ER )‐positive breast cancer by analyzing mutations and copy number variants ( CNV ), and by applying expression profiling. The whole exome and transcriptome of 47 Korean young breast cancer ( KYBR ) patients (age <35) were analyzed. Genomic profiles were constructed using mutations, CNV and differential gene expression from sequencing data. Pathway analyses were also performed using gene sets to identify biological processes. Our data were compared with young ER + breast cancer patients in The Cancer Genome Atlas ( TCGA ) dataset. TP 53 , PIK 3 CA and GATA 3 were highly recurrent somatic mutation genes. APOBEC ‐associated mutation signature was more frequent in KYBR compared with young TCGA patients. Integrative profiling was used to classify our patients into 3 subgroups based on molecular characteristics. Group A showed luminal A‐like subtype and IGF 1R signal dysregulation. Luminal B patients were classified into groups B and C, which showed chromosomal instability and enrichment for APOBEC 3A/B deletions, respectively. Group B was characterized by 11q13 ( CCND 1) amplification and activation of the ubiquitin‐mediated proteolysis pathway. Group C showed 17q12 ( ERBB 2) amplification and lower ER and progesterone receptor expression. Group C was also distinguished by immune activation and lower epithelial‐mesenchyme transition ( EMT ) degree compared with group B. This study showed that integrative genomic profiling could classify very young patients with breast cancer into molecular subgroups that are potentially linked to different clinical characteristics.