Molecular characterisation of cell line models for triple-negative breast cancers

Anita Grigoriadis*, Alan Mackay, Elodie Noel, Pei Jun Wu, Rachel Natrajan, Jessica Frankum, Jorge S. Reis-Filho, Andrew Tutt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Background: Triple-negative breast cancers (BC) represent a heterogeneous subtype of BCs, generally associated with an aggressive clinical course and where targeted therapies are currently limited. Target validation studies for all BC subtypes have largely employed established BC cell lines, which have proven to be effective tools for drug discovery.

Results: Given the lines of evidence suggesting that BC cell lines are effective tools for drug discovery, we assessed the similarities between triple-negative BCs and cell lines, to identify in vitro representatives, modelling the diversity within this BC subtype. 25 BC cell lines, enriched for those lacking ER, PR and HER2 expression, were subjected to transcriptomic, genomic and epigenomic profiling analyses and comparisons were made to existing knowledge of corresponding perturbations in triple-negative BCs. Transcriptional analysis segregated ER-negative BC cell lines into three groups, displaying distinctive abundances for genes involved in epithelial-mesenchymal transition, apocrine and high-grade carcinomas. DNA copy number aberrations of triple-negative BCs were well represented in cell lines and genes with coordinately altered gene expression showed similar patterns in tumours and cell lines. Methylation events in triple-negative BCs were mostly retained in epigenomes of cell lines. Combined methylation and gene expression analyses revealed a subset of genes characteristic of the Claudin-low BC subtype, exhibiting epigenetic-regulated gene expression in BC cell lines and tumours, suggesting that methylation patterns are likely to underpin subtype-specificity.

Conclusion: Here, we provide a comprehensive analysis of triple-negative BC features on several molecular levels in BC cell lines, thereby creating an in-depth resource to access the suitability of individual lines as experimental models for studying BC tumour biology, biomarkers and possible therapeutic targets in the context of preclinical target validation.

Original languageEnglish
Article number619
Number of pages14
JournalBMC GENOMICS
Volume13
DOIs
Publication statusPublished - 14 Nov 2012

Keywords

  • Microarray
  • Gene expression profiling
  • Comparative genomic hybridisation
  • Methylation arrays
  • Triple negative
  • Breast cancer
  • SITU HYBRIDIZATION ANALYSIS
  • MAMMARY EPITHELIAL-CELLS
  • BASAL-LIKE
  • IN-SITU
  • STEM-CELLS
  • EXPRESSION
  • TUMORS
  • SUBTYPES
  • CARCINOMAS
  • MICROARRAY

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