Abstract LB194: Analysis of Hippo/YAP abnormalities in head and neck cancer
Authors: Reyes German Velez , Wuertz Beverly , Ondrey Frank G. 
Published: July 2021

Introduction: Squamous cell carcinomas (HNSCC) comprise more than 95% of all head and neck cancers. Over the past decades the incidence and mortality rates of HNSCC have been steadily increasing worldwide. HNSCCs account for 6% of all human cancers and for 3% of all cancers in the United States. Leukoplakia, also known as smoker's keratosis are described as non-cancerous, pre-malignant inflammatory patches is a major risk factor in the development of HNSCC. In fact, up to 31% of all leukoplakias are believed to transform into HNSCC. Our interest into the molecular contributions to head and neck carcinogenesis has led us to follow up intriguing findings on the contributions of Yes Associated Protein (YAP) pathways that were found to upregulate proliferation, invasion/migration, and survival in head and neck cancer. More recent studies have found that Hippo/Yap activation occurs in many human cancers as well.

Materials and Methods: We performed several in silico analyses of available human cancer genetic data. We interrogated data from various Head and Neck Cancer studies. Specifically, we included data from the Recurrent and Metastatic Head & Neck Cancer (MSKCC, JAMA Oncol 2016), Head and Neck Squamous Cell Carcinoma (Broad, Science 2011), Head and Neck Squamous Cell Carcinoma (Johns Hopkins, Science 2011), Head and Neck Squamous Cell Carcinoma (TCGA, PanCancer Atlas), and the Oral Squamous Cell Carcinoma (MD Anderson, Cancer Discov 2013) using CBioPortal web tool. We explored factors responsible for Hippo pathway activation via loss of negative regulators or amplification of Hippo drivers. Results: We found many negative regulators, such as TAOK1, LATS1/2, among others to be mutated, exclusive of FAT1 loss, a known event in HNSCC. We also found amplification of YAP1, a driver of the Hippo pathway. We saw a loss of FAT1 in 22% of tumors, mutations in TAOK1 and LATS1/2 were seen in over 5% of tumors, exclusive of other mutations or gene expression derangements. YAP1 amplification was observed in up to 5% of tumors. Conclusions: These findings substantiate earlier findings where the YAP pathway was found to be upregulated in head and neck cancer subsets. Intriguingly, the loss of negative regulators or amplification of oncogenes, such as YAP1, likely contribute to Hippo/YAP upregulation. Since they are important pathways that may be activated at the crux of oral carcinoma in situ/invasion, findings from our in silico interrogation shed light on genetic abnormalities that probably occur earlier in the carcinogenesis spectrum. Further interrogation of leukoplakia preclinical models or data sets could shed additional light on contributions of Hippo/YAP to oral carcinogenesis.

Citation Format: German Velez Reyes, Beverly Wuertz, Frank G. Ondrey. Analysis of Hippo/YAP abnormalities in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB194.