Abstract LB-B25: Consensus tissue-independent epithelial tumour subtypes and their differing responses to therapy

Abstract

Background: Epithelial cancers are highly heterogeneous, and each epithelial tumour is composed of a number of subtypes. It is becoming clear that the same dysregulated pathways are common to different tumours, regardless of their tissue of origin. Therefore, the goal of the current study was to identify intrinsic tissue-independent epithelial tumour subtypes by analysing a large cohort of different epithelial tumours.

Methodology: Different gene expression profiles from various epithelial tumours (n = ∼5000) and cell lines (n = ∼200) from 12 different organs were merged using distance weight discrimination analysis, followed by consensus clustering using non-negative matrix factorization (NMF). The association of subtypes with response to various therapeutic compounds was identified using publicly available cell line drug response data.

Results: Three to seven consensus gene expression subtypes were identified and validated in the epithelial tumours and cell lines, irrespective of the tissue of origin. Certain epithelial subtypes were not present in melanoma or haematological cancers. The consensus subtypes had gene expression and biological profiles similar to normal epithelial and stem cells, and could be readily compared to the transcriptomic subtypes previously reported for individual epithelial tumour types. Moreover, specific gene signatures were identified that would be suitable as clinical assays in future applications of this classification system. There were significant differential responses between subtypes to different therapeutic compounds.

Conclusion: Several consensus transcriptomic subtypes were identified that are applicable to different organ-specific tumours. This study provides new avenues for precision therapy irrespective of the tissue of origin.

Late-Breaking Poster Session C:[xx]Animal Models

Citation Format: Anguraj Sadanandam. Consensus tissue-independent epithelial tumour subtypes and their differing responses to therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B25.