Study: JGAS00000000095




TitleHigh-coverage whole-genome sequencing reveals structural variations in triple-negative breast cancer
AbstractTriple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors or human epidermal growth factor receptor 2 (HER2). Currently, apart from poly ADP-ribose polymerase (PARP) inhibitors, there are few effective therapeutic options for this cancer type. Here, we present a comprehensive characterization of genetic alterations in TNBC via high-coverage whole-genome sequencing along with transcriptomic and whole-exome sequencing. Silencing of BRCA1 gene impaired the homologous recombination (HR) pathway in a subset of TNBC, which exhibited similar phenotypes with tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication. Clonal analysis suggested that TP53 mutations and methylation of CpG dinucleotides in the BRCA1 promoter were the early events of carcinogenesis. SVs were associated with driver oncogenic events such as amplification of MYC, NOTCH2 or NOTCH3 and impacted tumor suppressor genes including RB1, PTEN and KMT2C. We also identified a variety of oncogenes that could transform 3T3 mouse fibroblast cells, suggesting that individual TNBC tumors may undergo a unique driver event that can be targetable. Thus, we revealed several features of TNBC that had important clinical implications.
Study Type 1
Study TypeWhole Genome Sequencing
Study Type 2
Study TypeExome Sequencing
Study Type 3
Study TypeTranscriptome Sequencing

Study Attribute

NBDC Numberhum0094
Registration date2017-02-22
Submitting organizationDepartment of Celluar Signaling, Graduate School of Medicine, The University of Tokyo
Principal InvestigatorHiroyuki Mano
Molecular Data TypeWhole Genome Sequencing
Molecular Data TypeWhole Exome Sequencing
Molecular Data TypeRNA Sequencing
Primary PhenotypeTriple negative breast cancer
DiseaseTriple negative breast cancer
Sequencing methodWhole genome sequencing
Accession Title Dataset type Data objects Policy
JGAD00000000095 Bam and fastq files of TNBC Whole genome sequencing 159 JGAP00000000001