Characterization of MAD2B and other mitotic spindle checkpoint genes

Aneuploidy is a characteristic of the majority of human cancers, and recent work has suggested that mitotic checkpoint defects play a role in its deve lopment. To further explore this issue, we isolated a novel human gene, MAD 2B (MAD2L2), which is homologous to the spindle checkpoint gene MAD2 (MAD2L 1). We determined the chromosomal localization of it and other spindle chec kpoint genes, including MAD1L1, MAD2, BUB3, TTK (MPS1L1), and CDC20. In add ition, we resolved the genomic intron-exon structure of the human BUB1 gene . We then searched for mutations in these genes in a panel of 19 aneuploid colorectal tumors. No new mutations were identified, suggesting that genes yet to be discovered are responsible for most of the checkpoint defects obs erved in aneuploid cancers. (C) 1999 Academic Press.