Abstract 1213: Clinicopathological significance of ALK alterations in colorectal carcinoma.

Abstract

Abstract ALK has been shown to be a putative oncogene in lung cancer and neuroblastoma that can be potentially targeted with selective inhibitors. Ongoing clinical trials using ALK inhibitors such as Crizotinib have shown promising results. ALK gene copy gain number in colorectal cancer (CRC) patients have been shown to be associated with tumors that have a more aggressive phenotype. We investigated the alterations in ALK gene by FISH analysis, immunohistochemistry and screened for ALK mutations by sequencing the ALK gene in 737 CRC. We screened for mutations in ALK by sequencing the tyrosine kinase domain that covers exons 20 -28. ALK alterations were correlated with tumor pathological features including TNM staging, MSI status, KRAS and BRAF mutations, as well as clinical outcome. Overall survival was analyzed using Kaplan Meyer plots. On FISH analysis in colorectal cancers, ALK amplifications were observed in 2.6%. Amplifications and gain with increase in gene copy number(4 to 6 copies) were seen in 3.4%. No translocations were seen in our study. There were no associations with nodal metastasis and other clinical or molecular parameters. However in Stage III & IV, ALK amplification was associated with KRAS mutations. CRC subgroup with ALK amplifications showed a poor overall survival overall survival and ALK gene amplifications was an independent prognostic marker in multivariate Cox proportional Hazards model. IHC showed cytoplasmic overexpression in 14.7% CRCs and no associations with any clinical or molecular parameters. We are screening for ALK mutations in 100 CRC samples and results are awaited. The insights gained from our current study and future clinical trials are likely to directly benefit subgroups of CRC patients whose tumors are driven by ALK and will pave the way to more targeted approaches to cancer treatment. Citation Format: Zeenath Jehan, Sarita Esther Prabhakaran, Rong Bu, Nasser Al-Sanea, Alaa Abduljabbar, Luai Ashari, Samar Al-Homoud, Fouad Al Dayel, Shahab Uddin, Prashant Bavi, Khawla Sami Al-Kuraya. Clinicopathological significance of ALK alterations in colorectal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1213. doi:10.1158/1538-7445.AM2013-1213