Abstract 64: Abnormal splicing events in adenoid cystic carcinoma

Abstract

Abstract Salivary gland adenoid cystic carcinoma (ACC) is a relatively rare and understudied malignancy. While this disease can often be controlled locally by surgery and radiation therapy, distant metastases occur in nearly 50% of cases. Interestingly, these metastases can remain asymptomatic for several years, and there are currently no factors that are known to contribute to their dormancy or aggressiveness. Furthermore, there are no targeted chemotherapeutic agents available to treat any stage of this disease. To identify aberrations that contribute to ACC tumorigenesis, we performed whole genome methylation profiling, RNA sequencing, and exome sequencing on 18 primary ACC tumors and matched normal salivary gland tissue. A novel analysis methodology of Splice Expression Variability Analysis (SEVA) coupled with outlier statistical analyses of mRNA splice junctions revealed the presence of several abnormal splicing events (ASEs) in the studied tumors. Interestingly, the ASEs were significantly overrepresented in tumors as compared to matched normal salivary gland tissue. In vitro analyses found that many of the ASEs are also expressed in the only validated ACC cell line, MDA-ACC01, and multiple patient-derived xenograft (PDX) models of ACC. Overall, these studies have identified an unanticipated aberration in ACC and developed a model in which to study ASEs. Future work will be aimed at determining the functional impact that ASEs have on tumor initiation and growth. Citation Format: Brandon Leonard, Joseph O. Humtsoe, Hyun-Su Kim, Shizhang Ling, Luigi Marchionni, Elana J. Fertig, Michael Considine, Patrick Ha. Abnormal splicing events in adenoid cystic carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 64.