Human colon cancer cells deficient in DCC produce abnormal transcripts in progression of carcinogenesis

Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may b e superior to lymph node status in predicting patient survival for intermed iate stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting DCC would be ideal as a prognostic indicator. DCC is an alternat ively spliced molecule; thus, reliability of a PCR test for DCC will depend on amplifying only those regions of the molecule that are lost in the prog ression of colon cancer. For this reason, we studied a colon cancer cell li ne model at different stages of tumor progression to determine the alternat ive splice pattern for DCC. A commercially available colon cancer cell line system at different stages of tumor progression was used to identify which DCC exons are lost by western blot analysis, PCR, and RT-PCR techniques. C olon cancers express abnormal DCC transcripts. The proximal and distal exon s are present (exons 2 and 28-29). Exons located in the center of the molec ule are absent (6-7 and 18-23). This correlated to DCC protein loss in the cell lines. For clinical utility as a disease marker, exons in the middle p ortion of the DCC molecule that are spliced out should be utilized. Amplifi cation of the proximal and distal regions will result in falsely concluding that DCC is present when its protein product is not expressed.