Quantitative trait locus analysis of tumor morphology in a mouse model of human colorectal cancer
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AbstractColorectal cancer (CRC) is the second leading cause of cancer death in the United States. Early detection has frequently been cited as contributing to a favorable outcome. However, detection of CRC is impacted by tumor morphology, with the classical polypoid lesions being detected at a much higher rate than flat lesions. Recently, mouse models of CRC that consistently and almost exclusively develop flat lesions have been developed, indicating that specific host genetic modifiers exist that influence tumor morphology. Using the azoxymethane (AOM) model of human CRC we find that I/LNJ mice develop approximately 85% flat tumors while KK/HlJ mice develop approximately 85% polypoid tumors. To determine what genetic factors contribute to these phenotypic differences, we established an F2 genetic cross between these two mouse strains consisting of 119 animals. After a standardized AOM treatment regimen, these mice developed approximately 40% flat tumors. The mice were genotyped at 80 SNP's evenly spaced across the genome. Statistical analysis revealed two suggestive QTL for tumor morphology, one located on chromosome 12 (LOD 3.45) and the other on chromosome 9 (LOD 2.67). Follow up work has begun to fine map and identify candidate genes at these QTL through high dense SNP genotyping in an additional 300 F2 animals and eQTL analysis of normal colon tissue. These results indicate that tumor morphology is controlled by host genetic factors and we anticipate future studies focusing on the identification of these factors for development of therapeutic interventions.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 2126.
