Infrequent inactivation of DCC gene in replication error-positive colorectal cancers.

Colorectal cancers with and without the replication error (RER) exhibit fundamental differences in genotype and phenotype. While alterations in APC, p53, and K-ras genes have been characterized between RER+ and RER- colorectal cancers, the status of deleted in colorectal carcinomas (DCC) gene has not been yet. Alterations of DCC gene were analyzed in stage-matched two panels of 30 RER+ and 30 RER- colorectal cancers using semiquantitative reverse transcription-PCR and PCR-LOH analyses. Loss or reduction of DCC mRNA expression and allelic loss at the DCC locus were significantly less frequent in RER+ cancers than in RER- cancers. Interestingly, reduced DCC mRNA expression was observed in all 5 RER- cancers with liver metastasis. Our results support the concept that RER+ and RER- colorectal cancers represent different pathways of carcinogenesis and may give a hint for clarifying the specific mechanism of DCC inactivation in RER- colorectal cancers.