Mutation in the nm23 Gene Is Associated with Metastasis in Colorectal Cancer1

The human nm23 gene, a candidate metastatic suppressor gene, consists of two genes, nm23-Hl and nm23-H2. The potential mutation in the nm23-HI gene was examined in colorectal cancer using a reverse tran scription polymerase chain reaction amplification followed by DNA se quencing analysis. Genomic alterations in the nm23 gene were also exam ined by Southern hybridization. Genetic alterations either as a deletion in the coding sequence of nm23-Hl or as an allelic deletion were detected in four among eight colorectal adenocarcinomas associated with métastases in lymph nodes, lung, or liver. No alteration was observed in 12 additional colorectal cancer specimens without metastasis. These results provide first evidence for novel mutation in the nm23 gene and demonstrate a corre lation between the mutation in the nm23 gene and metastasis in colorectal oncogenesis which suggests that the «/«-'.) gene plays a role in the causa