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Background  Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of  SEPT9  and  SHOX2  has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions.    Results  Assessment of promoter methylation of  SEPT9  distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (all  p  < 0.001). Correspondingly,  SHOX2  methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues ( p  < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the  SEPT9  gene locus.    Conclusions   SEPT9 / SHOX2  methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.

SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas