High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk.
Evidence based on Bub1 mutations in colorectal cancers suggests it might be a driving force in tumorigenesis via generation of chromosomal instability (CIN) and aneuploidy.
Chromosomal instability in colorectal cancers is associated with functional loss of a mitotic check point partly due to mutations of the Bub1, one of the mitotic check point genes.
This result suggests that the inactivation of hBUB1 may be very rare in human carcinomas, or restricted to certain cell lines of colorectal carcinomas.
Two related protein kinases and homologues of the yeast checkpoint genes, hBUB1 and hBUB1B, have been implicated in the pathogenesis of colorectal cancers.
Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate that mutations in BUB1 are rare causes of chromosome instability in CRC or NSCLC.