title: A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T.
abstract: To determine sequence variations of the BUB1 and BUB1B genes in pancreatic cancer, the entire coding regions of the BUB1 and BUB1B genes were sequenced in pancreatic cancer cell lines and xenografts. Although only polymorphic alterations were found in the BUB1B gene, the aneuploid pancreatic cell line Hs766T had two novel missense variants (p.[Y259C;H265N]) in the BUB1 gene. These mutations were on the same allele, accompanied by a wild-type BUB1 allele. This change was not found in other samples, the literature, or 110 additional chromosomes from a reference population. Compared to two cell lines having microsatellite instability (MIN), the TP53 wild-type pancreatic cell line Hs766T had a defective mitotic spindle checkpoint, indicative of a cell line with chromosomal instability (CIN). Evidence that this checkpoint pathway can be abrogated by mutations in the BUB1 gene (Cahill et al., 1998) supports the suggestion the missense mutations of the BUB1 gene in the Hs766T cell line may contribute to its observed mitotic checkpoint defect.
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hempen
authors.forename: Harsha
authors.initials: H
authors.lastname: Kurpad
authors.forename: Eric S
authors.initials: ES
authors.lastname: Calhoun
authors.forename: Susan
authors.initials: S
authors.lastname: Abraham
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000473:pathology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D017422:Sequence Analysis, DNA / Q000379:methods; D008941:Spindle Apparatus / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases