Abstract 4919: Pathway profiling of head and neck cancer cell lines

Abstract

Abstract Introduction: Cell lines retain key genetic aberrations of the originating tumors, which frequently correlate with sensitivity to specific inhibitors. We performed genetic and pathway based profiling of 40 head and neck cancer (HNC) cell lines using three publicly available methods for pathway profiling based on expression and copy number data. Methods: 40 HNC cell lines were analyzed for expression using expression arrays (Agilent), and copy number using array comparative hybridization (aCGH) and/or Nanostring methodologies. Integrative genomic analysis was performed to determine pathway activity using pathway analysis techniques previously described by Gatza et al. (BFRM), Pe'er et al (CONEXIC), Vaske et al. (PARADIGM). Results: Frequent pathway activation was identified in >10 well established signalling pathways for HNC including TP53, PI3K-AKT, TP63/SOX2, Cyclin D1, MYC etc, as well as several - for HNC previously unknown - signalling pathways. Cell lines could be associated with expression-based biologic subtypes in HNC tissues suggesting that specific cell lines should be used preferentially for modelling and therapeutic evaluation for HNC subtypes (including HPV(+) cell lines with characteristics of HPV(+) tumors). The three pathway analysis platforms identified a large number of pathways with some overlap in particular between BFRM and CONEXIC, whereas PARADIGM profiled a much wider set of pathways. Both CONEXIC and PARADIGM employed copy number data, whereas BFRM relied solely on expression data. Conclusion: Pathway alterations characteristic of head and neck cancers were identified in virtually all HNC cell lines. Pathway based classification of cell lines was achieved and correlated with pathway activity in HNC tumor tissues. Three pathway-profiling approaches provided a large set of pathway activity with some significant overlap that may have translational relevance. Validation studies are currently on-going. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4919. doi:1538-7445.AM2012-4919