Abstract 2453: Chromatin remodeling genes are frequently somatically altered in cervical carcinomas

Abstract

Abstract Introduction: Cervical cancer is responsible for 15% of all deaths due to cancer in women worldwide. There is a need to identify somatic mutations driving this cancer in order to facilitate development of novel therapeutic strategies. Experimental procedures: We analyzed whole exome sequencing data from 430 cervical carcinomas. The data were derived from a combination of our previously published work (Ojesina et al. Nature 2014; Chung et al, Int J Cancer 2015), and publicly available data generated by the Cancer Genome Atlas (TCGA). The Mutect2.0 and MutSig2CV algorithms were used to identify somatic mutations and significantly mutated genes (SMGs) respectively. Copy number alterations were analyzed using the GISTIC algorithm. Findings: Based on MutSig2CV false discovery rate threshold of 0.1, we identified MLL3 (19%) and MLL2 (13%) as novel significantly mutated genes (SMGs) in cervical cancer. In addition, other chromatin modifying genes including EP300 (12%) and ARID1A (7%) were confirmed as SMGs. Further investigation of genes that did not meet the threshold revealed that 228 of 430 (53%) of cervical tumors harbored at least one somatic mutation in a chromatin modifying gene. These include genes in the myeloid/lymphoid or mixed-lineage leukemia (MLL) family (28%), lysine (K)-specific demethylase (KDM) family (23%), AT rich interactive domain (ARID) family (13%), SWI/SNF related, matrix associated, actin dependent regulator of chromatin (SMARC) family (8%) and histone cluster 1 (HIST1) family (4%). Conclusions: We have demonstrated that a majority of cervical cancers harbor somatic mutations in chromatin remodeling genes. This novel finding was facilitated by the larger sample size derived from combining multiple datasets, and may have diagnostic and therapeutic implications in cervical cancer. Citation Format: Akinyemi Ojesina, Aishwarya Sundaresan, Vinodh Srinivasasainagendra, Hemant Tiwari, Warner Huh. Chromatin remodeling genes are frequently somatically altered in cervical carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2453. doi:10.1158/1538-7445.AM2017-2453