Abstract B116: Molecular profiling of breast cancer cell lines using signatures reported in prognostic and predictive patient studies
Authors: Sninsky John , Kwok Shirley , Wang Alice , Kim Wontae , Lagier Robert , Christopherson Cindy , Rowland Charley , Waldman Fred , Tutt Andrew , Broder Sam , Esserman Laura , Benz Chris 
Published: June 2012

Background: Breast cancer cell lines recapitulate complex tumors in humans and have been widely used to shed light on oncogenesis and characterize the response to established and new therapeutics. Gene signatures may be used to assess which oncogenic pathways are deregulated in breast cancer cells and to guide targeted therapy. Browser-based access to CGH and expression array profiles has begun to provide systems biology information on these cell lines. Since RT-PCR is increasingly being used to profile gene signatures in patient breast cancer tumors and due to often observed discordance between arrays and RT-PCR, we embarked on a translational study to profile the expression levels of constituent genes and derived scores of reported signatures in commonly used breast cancer cell lines.

Methods: RNA from 47 cell lines with substantial overlaps with cell line collections reported by Neve et al. (36/51), Kao et al. (36/52) and the Integrated Cancer Biology Program (ICBP-45) (43/45) was profiled using RT-PCR for individual genes of the signatures reported by Paik et al. (21-gene Recurrence Score and subset gene groups), Tutt et al (14-gene metastasis score), and Teschendorff and Caldas (7-gene immune response score). The relative changes in gene expression were calculated as previously described. Individual gene and group weightings were as reported.

Results: The 14-gene metastasis signature was highly correlated with the Proliferation Group of the Recurrence Score (r2=0.78). In ER positive cell line subset analysis, this same comparison resulted in r2=0.72. The ER Group of the Recurrence Score was correlated to the overall Recurrence Score (r2=0.65) and highly correlated to the level of the progesterone receptor (r2=0.82). The HER2 mRNA level alone was highly correlated to the HER2 Group of the Recurrence Score (r2=0.73). The metastasis score differentially-weighted with the hormone receptor levels was correlated with the Recurrence Score (r2=0.70). The 7-gene immune response gene set was not correlated with proliferation indices or composite scores in the combined or ER-negative cell line collections. Correlations with the luminal and basal tumor subtypes required composite scores of proliferation, HER2 and hormone receptor status.

Conclusion: Breast cancer cell lines of commonly used collections have an elevated and continuous range of molecular proliferation indices as determined by groups of genes in signatures reported in community and randomized control trial settings. Even though sharing only a limited number of genes, composite scores encompassing proliferation, hormone receptors and growth factor RNA levels are similar. Gene sets focused on immune response may provide discrete additional information. Knowledge of pharmacologic responses of these cell lines to established and new therapeutics with associated subgroup and derived overall scores may contribute to our understanding of the discrete oncologic pathways involved and inform future individualized patient management.

Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B116.