Abstract 2881: Systemic Chromosome Instability (CIN) resulted in transcriptomic changes in metabolic and proliferation regulators in colonic mucosal tissue of Sgo1-/+ mice

Abstract

Abstract (a) Colon cancer is the second most lethal cancer and is predicted to claim 50,310 lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon cancers and is thought to contribute to colon cancer progression and recurrence. We developed animal models focusing on mitotic error-induced CIN, Shugoshin-1 (Sgo1) haploinsufficient (-/+) mice, to investigate the impact of CIN on colon cancer development. Sgo1-/+ mice showed altered profiles in colonic lesions and cancer development. In this study, we analyzed signature changes in the colonic transcriptome of Sgo1-/+ mice to investigate underlying molecular events in the altered carcinogenesis profiles. (b) We treated control and Sgo1-/+ mice with colonic carcinogen azoxymethane (AOM), and tracked colon cancer development 12, 24, and 36 weeks after AOM treatments. We performed Next Generation Sequencing (NGS)-based transcriptome analysis at 24 weeks. (c) There were 349 hits with 2-fold expression difference threshold, P<0.05 (217 upregulated genes, 132 downregulated genes). In normal-looking colonic mucosal tissue from Sgo1 mice, we observed notable transcriptomic changes in the lipid metabolism, Notch signaling, insulin signaling, and peroxisome proliferator-activated receptor (PPAR) pathways. The profile had partial overlap with the colon tumor transcriptome, consistent with high prevalence of CIN in colon cancer. By applying secondary selection criteria, we also identified cell surface markers that may be used to selectively target colonic CIN cells with antibody-based or vaccine approaches. (d) Systemic Chromosome Instability resulted in transcriptomic changes in metabolic and proliferation regulators in the colon. We propose that the CIN effect may be countered through manipulation of these pathways. Citation Format: Chinthalapally V. Rao, Saira Sanghera, Yuting Zhang, Laura Biddick, Arun Reddy, Stan Lightfoot, Altaf Mohammed, Wei Dai, Hiroshi Y. Yamada. Systemic Chromosome Instability (CIN) resulted in transcriptomic changes in metabolic and proliferation regulators in colonic mucosal tissue of Sgo1-/+ mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2881. doi:10.1158/1538-7445.AM2015-2881