Abstract PR08: Systematic pan-cancer analyses of Hippo pathway deregulation in cancer

Hippo signaling is a highly conserved, pleiotropic pathway that is recurrently deregulated across many cancers. With large-scale cancer genomics data, several efforts have been undertaken to quantify Hippo pathway activity in an unbiased manner. However, identifying a comprehensive catalog of Hippo pathway genes can be difficult due to the heterogenous nature of the disease and the limitations of any given study. Here we show the high concordance between different methods of quantifying Hippo pathway activity in cancers. Furthermore, we establish a first-principled approach by experimentally deriving a lineage-independent quantification by leveraging the transcriptomic profiles of nearly 900 cell lines from 28 tissue types. We applied these signature(s) to the genomic profiles of over 11,000 primary human cancer patients to identify several statistically significant biomarkers associated with Hippo pathway dysregulation, including NF2 mutations and deletions, SOX2 amplifications, and CDH1 mutations. To further assess therapeutic implications of pathway inhibition, we applied machine learning approaches to predict a tumor’s sensitivity to Hippo pathway inhibition based on its genomic profile, revealing that Hippo pathway inhibition may be a tractable approach in a wide spectrum of cancers. This abstract is also being presented as Poster B38. Citation Format: Matthew T. Chang, Thijs J. Hagenbeek, Jennifer Lacap, Zora Modrusan, Christiaan Klijn, Anwesha Dey. Systematic pan-cancer analyses of Hippo pathway deregulation in cancer [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr PR08.