title: Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer.
abstract: Genomic instability is observed in the majority of human tumors. Dysregulation of the mitotic spindle checkpoint is thought to be one of the mechanisms that facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint kinase BLUB1 cause a dominant negative disruption of the spindle, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1 locus was evaluated in 32 colorectal cancer (CRC) and 20 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 analysis. The 2q locus was allelically stable in NSCLC but relatively unstable in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BUB1 mutations and polymorphisms were rare (< 1%) in the CRC or NSCLC tumors. 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. Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression.
authors.affiliation: Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Scotland.
authors.forename: R G
authors.initials: RG
authors.lastname: Jaffrey
authors.forename: S C
authors.initials: SC
authors.lastname: Pritchard
authors.forename: C
authors.initials: C
authors.lastname: Clark
authors.forename: G I
authors.initials: GI
authors.lastname: Murray
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: K M
authors.initials: KM
authors.lastname: Kerr
authors.forename: M C
authors.initials: MC
authors.lastname: Nicolson
authors.forename: H L
authors.initials: HL
authors.lastname: McLeod
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases