Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer

Genomic instability is observed in the majority of human tumors. Dysregulat ion of the mitotic spindle checkpoint is thought to be one of the mechanism s that facilitate aneuploidy in tumor cells. Mutations in the mitotic spind le checkpoint kinase BUB1 cause a dominant negative disruption of the spind le, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in hum an tumors. The BUB1 locus mas evaluated in 32 colorectal cancer (CRC) and 2 0 non-small cell lung cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for 2q, two CA repeats in BUB1, and gene mutation an alysis, The 2q locus mas allelically stable in NSCLC but relatively unstabl e in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BU B1 mutations and polymorphisms were rare (<1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate th at mutations in BUB1 are rare causes of chromosome instability in CRC or NS CLC, Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and p rogression.