title: Characterization of MAD2B and other mitotic spindle checkpoint genes.
abstract: Aneuploidy is a characteristic of the majority of human cancers, and recent work has suggested that mitotic checkpoint defects play a role in its development. To further explore this issue, we isolated a novel human gene, MAD2B (MAD2L2), which is homologous to the spindle checkpoint gene MAD2 (MAD2L1). We determined the chromosomal localization of it and other spindle checkpoint genes, including MAD1L1, MAD2, BUB3, TTK (MPS1L1), and CDC20. In addition, we resolved the genomic intron-exon structure of the human BUB1 gene. We then searched for mutations in these genes in a panel of 19 aneuploid colorectal tumors. No new mutations were identified, suggesting that genes yet to be discovered are responsible for most of the checkpoint defects observed in aneuploid cancers.
authors.affiliation: Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21231, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Cahill
authors.forename: L T
authors.initials: LT
authors.lastname: da Costa
authors.forename: E B
authors.initials: EB
authors.lastname: Carson-Walter
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: C
authors.initials: C
authors.lastname: Lengauer
mesh_terms: D000595:Amino Acid Sequence; D003110:Colonic Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers; D016208:Databases, Factual; D005091:Exons; D006801:Humans; D007438:Introns; D064246:Mad2 Proteins; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D011506:Proteins