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Characterization of MAD2B and Other Mitotic Spindle Checkpoint Genes
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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.
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“Hence, our results provide one explanation for why loss-of-function mutations in spindle checkpoint genes are uncommon in human cancers 11,12 .”
From Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control (2004) · cites this paper as [11]
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“loss-of-function mutations in spindle checkpoint genes are rarely observed in human tumours 11,12 .”
From Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control (2004) · cites this paper as [11]
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Metadata
- Authors
- Cahill, D. P., da Costa, L. T., Carson-Walter, E. B., Kinzler, K. W., Vogelstein, B., & Lengauer, C.
- Affiliations
- Johns Hopkins University (US)
- Howard Hughes Medical Institute (US)
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 58
- Issue
- 2
- Pages
- 181-187
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W1970916591
- Cited by
- 212
- References
- 36
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 7 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 1 · 2013: 6 · 2012: 6
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genomics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA62924, CA43460)
- National Cancer Institute (CA43460, P50CA062924, CA 62924)
- National Institute of General Medical Sciences (T32GM007184, GM07184)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- MAD2L2, mitotic spindle checkpoint, aneuploidy, colorectal cancer, chromosomal localization, gene structure, BUB1, Bub3, TTK, CDC20, MAD1L1, Mad2
- MeSH terms
- Amino Acid Sequence, Colonic Neoplasms, DNA Mutational Analysis, Exons, Humans, Introns, Spindle Apparatus, Molecular Sequence Data, Polymorphism, Genetic, Proteins, Tumor Cells, Cultured, Databases, Factual, Sequence Homology, Amino Acid, DNA Primers, Physical Chromosome Mapping, Mad2 Proteins
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