Abstract 2151: Molecular screening of CRC from India suggests the existence of non-canonical pathway(s) of tumorigenesis

Abstract

A major risk factor for Colorectal Cancer (CRC) is advanced age, with a majority of cases reported in the West being above 60 years of age. However, a significantly high proportion of CRC patients from India belong to a younger age group (less than 50 years) and a majority of them have no family history of cancer. A deregulated Wnt signaling pathway is the hallmark of CRC in the West and has been indicted in 70-80% of older patients. Another significant genetic aberration is Microsatellite Instability (MSI), which may contribute to 15-20% of the cases. In addition, the simultaneous occurrence of Wnt activation and p53 inactivation has been substantiated in a significantly high proportion (about 70%) of CRC cases. Sporadic CRC occurring in the young however has not been subjected to detailed analysis so far. In order to identify important deregulated pathways that drive tumor progression in young patients we have initiated a multipronged comparative study on CRC occurring in the young and older patients from India. Our results have revealed several unique features among Indian CRC patients. Firstly, Wnt activation and p53 inactivation appeared to co-exist in a significantly less proportion of samples (34%), indicating existence of alternate pathway(s) of tumor initiation. Secondly, a significantly low proportion (35%) of young patients appeared to harbor a deregulated Wnt signaling pathway, when compared to older patients (64%). Thirdly, we did not find a significant difference in other variables between the two patient age groups including gender, grade, MSI status, etc. Using array-based Comparative Genomic Hybridization (aCGH) and genome-wide transcript profiling, we identified several copy number alterations (CNA) that may harbor genes important for tumor progression in young patients. A novel amplification located at 17q11.2-21.1 was identified which included genes involved in the MAP kinase pathway. The present study is expected to yield invaluable insights into the molecular basis for sporadic CRC in the young. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2151.