Abstract 1708: LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer

Abstract

Abstract Introduction: Epigenetic alterations including hypermethylation of gene promoter regions and global hypomethylation of DNA are common in colorectal cancer (CRC). We recently reported that long interspersed nuclear element 1 (LINE-1) methylation level in tumor, a surrogate of global methylaiton, predicts prognosis and response to oral fluoropyrimidines of CRC patients. This suggests that the LINE-1 methylation level is a useful marker for tailored therapy in CRC. However, the LINE-1 methylation level in tumor may be heterogeneous because the DNA methylaion is reversible, which is a problem when the LINE-1 methylation level in tumor is used for decision making in clinic. In this study we investigated LINE-1 methylation level in cancer cells isolated from multiple tumor sites to evaluate intra-patient heterogeneity of the LINE-1 methylation level in tumor tissues. Methods: Primary tumor, metastatic lymph nodes, and distant metastases in 41 CRC patients were used for measurement of LINE-1 methylation level. Cancer cells in primary tumors were collected from tumor center and invasion front by laser capture microdissection (LCMD). Cancer cells in metastatic lymph nodes and distant metastases were also collected by LCMD. The LINE-1 methylation level was measured by multicolor MethyLight assay following bisulfite modification of DNA and was correlated with clinicopathological parameters. Results: There was no significant difference in the LINE-1 methylation level between cancer cells from the center and those from invasion front of the primary tumor tissue. In the same patient, there was no significant difference in the LINE-1 methylation level between the samples from primary tumor, metastatic lymph nodes, and distant metastases. The LINE-1 methylation level was decreased as the tumor stage advances. Discussion: The results suggest that the LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer. Prediction of patients’ prognosis using LINE-1 methylation level may be possible by multiple tumor specimen such as biopsy specimen by colonoscopy and surgically resected tumor. Measuring LINE-1 methylation level in primary tumor may be useful for prediction of response to fluoropyrimidines in metastatic tumor. 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 1708. doi:1538-7445.AM2012-1708