Abstract 1412: Capturing c-Myb target genes in adenoid cystic carcinoma

Abstract

Abstract Mutated versions of c-Myb are potent oncoproteins, and Myb proteins are over- or highly-expressed in a wide variety of human tumors. Adenoid Cystic Carcinoma (ACC), the second most frequent malignancy of minor and major salivary glands, frequently contains a recurrent t(6;9) translocation which fuses the c-Myb proto-oncogene on chromosome 6q to the NFIB gene on chromosome 9p resulting in the expression of novel Myb-NFIB fusion oncoproteins. These variants of c-Myb play a definitive role in development of ACC tumors, and are the first evidence that Myb proteins function as “driver” mutations in human cancer. Identifying target genes directly regulated by Myb-NFIB oncoproteins in ACC tumors can help determine how Myb proteins transform cells and contribute to tumor development in ACC. Genomics analyses of solid tumors is challenging because tumors are often heterogeneous tissue types and are often not stored in a manner that preserves labile nucleic acids. FFPE samples offer the most promise since formaldehyde fixation effectively “locks” the Myb-NFIB fusion proteins and epigenetic marks, such as modified histones, to the genes of interest. We have developed improved methods were for extracting chromatin from FFPE samples for use in chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) and are applying these technical innovations to ACC tumors preserved in FFPE. When combined with gene expression information provided by RNA-seq analysis, ChIP-seq analysis of c-Myb gene targets will identify regulators that can be targets in novel therapeutic strategies in the future, as well as provide a greater understand of c-Myb functions in ACC and other epithelial tumors in which Myb plays a role. Citation Format: KATHRYN BRAYER, Scott Ness. Capturing c-Myb target genes in adenoid cystic carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1412. doi:10.1158/1538-7445.AM2014-1412