Mutational Inactivation of Mitotic Checkpoint Genes, hsMAD2 and hBUB1, Is Rare in Sporadic Digestive Tract Cancers

Genetic instability is a key mechanism of tumorigenesis, and the instability exists at two distinct levels, the nucleotide and the chromosome levels. Disruption of the mitotic spindle checkpoint is one of the underlying mechanisms leading to aneuploidy and alterations of hsMAD2 and hBUB1, assumed to take part in the spindle checkpoint in human cells, have been found to be associated with chromosomal instability in some tumor cell lines. Therefore, we investigated the mutational status of the hsMAD2 and hBUB1 genes in 32 sporadic digestive tract cancers by reverse transcription‐ polymerase chain reaction‐single strand conformation polymorphism analysis. The entire coding sequence of the hsMAD2 gene, and conserved regions (codons 21–152 and codons 732–1043) presumed to be functionally important in the hBUB1 gene were analyzed. Mutation of the hsMAD2 gene was not observed at all and missense mutation of the hBUB1 gene was noted in one rectal cancer case. Sequencing analysis revealed an AGT‐to‐GGT missense mutation, substituting glycine for serine, at codon 950, which is conserved between budding yeast and human. These results indicate that mutations of the hsMAD2 and hBUB1 genes are very rare and presumably play a very restricted role in tumor development of sporadic cancers.