Abstract 3105: Chromosome 18q encodes a chromosomal instability suppressor locus in colorectal cancer

Abstract

Abstract Identifying molecular mechanisms initiating Chromosomal Instability (CIN) may lead to approaches to limit intratumour heterogeneity and treatment failure in cancer. Here we identify candidate CIN-suppressor genomic loci that are subject to copy number loss in CIN colorectal cancers (CRCs). Genes encoded within CIN-suppressor loci were characterized through an RNA interference screen for induction of chromosome segregation errors in mitosis, revealing 5 CIN-suppressor genes encoded on chromosome 18q. CIN-suppressor gene silencing in chromosomally stable cells generates structurally abnormal chromosomes, which are missegregated during mitosis. A chromosome segregation error spectrum characteristic of structurally abnormal chromosomes is also observed in CIN CRC cell lines. 18q loss occurs in the majority of aneuploid CRCs, and is associated with both structural and numerical instability in colorectal tumours, and with aneuploidy onset in a rare carcinoma-in-adenoma dataset. These data support a role for chromosome 18q in the maintenance of chromosomal structural integrity and mitotic fidelity, and suggest that 18q copy number loss may initiate CIN during CRC development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3105. doi:1538-7445.AM2012-3105