title: Absence of aneuploidy and gastrointestinal tumours in a man with a chromosomal 2q13 deletion and BUB1 monoallelic deficiency.
abstract: Chromosomal instability is a potentially critical step in the development of colorectal cancer. The budding uninhibited by benzimidazole 1 (BUB1) gene is a highly conserved protein that plays a critical role at the spindle assembly checkpoint during cell division. BUB1 mutations function in a dominant-negative fashion and have been implicated in causing dysfunctional kinetochore attachments, premature chromatid separation, accelerated mis-segregation of whole chromosomes and aneuploidy. BUB1 mutations have been observed in patients with colorectal cancers. We report a remarkable case of BUB1 haploinsufficiency owing to a 1.7 Mb deletion of chromosome 2q13 in a 54-year-old man with no prior history of carcinoma. These mutant alleles were observed in both tissue from the hand and peripheral blood. Aneuploidy was not observed on cytogenetic analysis. These findings highlight the insufficiency of BUB1 haploinsufficiency to directly stimulate tumourigenesis, and suggest that other factors may be more critical to this process.
authors: Department of Surgery,  Yale University School of Medicine, New Haven, Connecticut,  USA.
authors: Don
authors: D
authors: Hoang
authors: Gloria R
authors: GR
authors: Sue
authors: Fang
authors: F
authors: Xu
authors: Peining
authors: P
authors: Li
authors: Deepak
authors: D
authors: Narayan
mesh_terms: D000483:Alleles; D000782:Aneuploidy; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D043171:Chromosomal Instability / Q000235:genetics*; D002872:Chromosome Deletion; D020090:Chromosome Segregation / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases