Somatic alterations of the DPC4 and Madr2 genes in colorectal cancers and relationship to metastasis

The DPC4 and Madr2 genes are located at 18q21, and the LOH on chromosome 18 q21 has been shown to occur frequently in colorectal cancers. To investigat e the role of these genes in advanced colorectal cancers, we analyzed 29 co lorectal specimens for alterations in the DPC4 and Madr2 genes. Twelve (63. 2%) of 19 informative primary colorectal cancers showed allelic loss of chr omosome 18q21.3 marker. An alteration of the DPC4 gene, sequence was identi fied in 6 (20.7%) of 29 colorectal carcinomas, and the distinct Madr2 gene mobility shifts were present in 3 (10.3%) cancers. Somatic mutations were i dentified in these tumors by sequencing analysis. DPC4 gene alterations of 4 cases were detected in Mad homology 2 domains. There was no significant c orrelation between the somatic alteration of Madr2 and clinicopathological findings. However, the frequency of DPC4 mutation was significantly higher in tumors associated with liver metastasis than in those without such metas tasis. Our findings suggest that somatic alteration of the DPC4 gene may pl ay a role in tumorigenesis and liver metastasis of human colorectal cancers .