Abstract A24: Functional annotation of the Hippo somatic mutations in human cancer

Abstract

Abstract The Hippo pathway plays a crucial role in organ size control and tissue homeostasis, whose downstream targets YAP and TAZ are frequently activated in various types of human cancers. However, inactivation of this key tumor suppressor pathway in human cancers has not been fully characterized. In this study, we comprehensively annotate the somatic mutations for 23 Hippo core components in The Cancer Genome Atlas, which includes 11,706 patient samples across 32 major human cancer types. To determine the role of these patient-derived mutations in Hippo pathway regulation, we reconstituted each Hippo component mutant into the corresponding knockout (KO) cells and performed an immunofluorescence screen by using YAP cellular localization as a readout. Through it, we identified a number of somatic mutations that are able to suppress Hippo signaling and activate YAP. In addition, we elucidated the underlying mechanism for several identified somatic mutations and revealed novel regulatory mechanisms for the Hippo pathway. Taken together, our study not only systematically profiled the somatic mutations for the Hippo pathway components, but also generated a valuable resource to further characterize of this key signaling pathway in human cancer development. Citation Format: Han Han, Wenqi Wang. Functional annotation of the Hippo somatic mutations in human 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 A24.