Abstract A1-28: Chromosome fusions triggered by noncoding RNA

Abstract

Abstract Chromosomal fusion is a frequent occurrence in cancer cells and can promote transformation through the generation of oncogenic gene products. There are two non-exclusive models for how these chromosome fusions may occur: (1) the instability of the cancer genome produces chromosomal fusions randomly and those promoting transformation enjoy a selective advantage, or (2) some non-random mechanism drives chromosome fusion. Evidence for (2) comes from recurrent fusion events and correlative human data linking noncoding RNA expression with chromosome fusion. To help address this important fundamental question, we functionally tested the role of noncoding RNA, specifically piRNAs, in promoting chromosomal fusion in the ciliate, Oxytricha trifallax, a microbial eukaryote. We microinjected custom piRNAs into cells and observed chromosome fusion in four cases (of four tested), including a double fusion event and a chromosome circularization event (self-fusion). Furthermore, these RNA-mediated inter-and-intra-chromosomal fusions are heritable over multiple sexual generations, illustrating the ability of noncoding RNAs to program genome architecture, including chromosome fusion and circularization. Citation Format: John Bracht, Xing Wang, Keerthi Shetty, Xiao Chen, Mariusz Nowacki, Sierra McCloud, Derek Clay, Laura Landweber. Chromosome fusions triggered by noncoding RNA. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-28.