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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer

Authors: Zi-Ming Zhao, Susan E. Yost, Katherine E. Hutchinson, Sierra Min Li, Yate-Ching Yuan, Javad Noorbakhsh, Zheng Liu, Charles Warden, Radia M. Johnson, Xiwei Wu, Jeffrey H. Chuang, Yuan Yuan

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Triple negative breast cancer (TNBC) is aggressive with limited treatment options upon recurrence. Molecular discordance between primary and metastatic TNBC has been observed, but the degree of biological heterogeneity has not been fully explored. Furthermore, genomic evolution through treatment is poorly understood. In this study, we aim to characterize the genomic changes between paired primary and metastatic TNBCs through transcriptomic and genomic profiling, and to identify genomic alterations which may contribute to chemotherapy resistance.

Methods

Genomic alterations and mRNA expression of 10 paired primary and metastatic TNBCs were determined through targeted sequencing, microarray analysis, and RNA sequencing. Commonly mutated genes, as well as differentially expressed and co-expressed genes were identified. We further explored the clinical relevance of differentially expressed genes between primary and metastatic tumors to patient survival using large public datasets.

Results

Through gene expression profiling, we observed a shift in TNBC subtype classifications between primary and metastatic TNBCs. A panel of eight cancer driver genes (CCNE1, TPX2, ELF3, FANCL, JAK2, GSK3B, CEP76, and SYK) were differentially expressed in recurrent TNBCs, and were also overexpressed in TCGA and METABRIC. CCNE1 and TPX2 were co-overexpressed in TNBCs. DNA mutation profiling showed that multiple mutations occurred in genes comprising a number of potentially targetable pathways including PI3K/AKT/mTOR, RAS/MAPK, cell cycle, and growth factor receptor signaling, reaffirming the wide heterogeneity of mechanisms driving TNBC. CCNE1 amplification was associated with poor overall survival in patients with metastatic TNBC.

Conclusions

CCNE1 amplification may confer resistance to chemotherapy and is associated with poor overall survival in TNBC.
Appendix
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Metadata
Title
CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer
Authors
Zi-Ming Zhao
Susan E. Yost
Katherine E. Hutchinson
Sierra Min Li
Yate-Ching Yuan
Javad Noorbakhsh
Zheng Liu
Charles Warden
Radia M. Johnson
Xiwei Wu
Jeffrey H. Chuang
Yuan Yuan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5290-4

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