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MIM.602860 15q15

Wednesday 21 March 2007

BUB1B gene encodes a key protein in the mitotic spindle checkpoint.

BUB1B and RASSF1A genes play specific roles in the mitotic checkpoint, and their defects may cause chromosome instability or aneuploidy in mouse fibroblasts and human cancer cell lines; however, few studies have reported a correlation between defects in these genes and chromosome changes in human tumor samples.


- germline mutations of BUB1B in

  • mosaic variegated aneuploidy syndrome (MVA syndrome)
  • premature chromatid separation (PCS) (MIM.176430)
    • heterozygous mutation in the BUB1B gene
    • autosomal dominant trait without phenotypic consequences

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses.

In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint, have been identified. (15475955)

These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development. (15475955)


- Haruta M, Matsumoto Y, Izumi H, Watanabe N, Fukuzawa M, Matsuura S, Kaneko Y. Combined BubR1 protein down-regulation and RASSF1A hypermethylation in Wilms tumors with diverse cytogenetic changes. Mol Carcinog. 2008 Feb 19; PMID: 18286482

- Scintu M, Vitale R, Prencipe M, Gallo AP, Bonghi L, Valori VM, Maiello E, Rinaldi M, Signori E, Rabitti C, Carella M, Dallapiccola B, Altomare V, Fazio VM, Parrella P. Genomic instability and increased expression of BUB1B and MAD2L1 genes in ductal breast carcinoma. Cancer Lett. 2007 Sep 8;254(2):298-307. PMID: 17498870

- Myslinski E, Gérard MA, Krol A, Carbon P. Transcription of the human cell cycle regulated BUB1B gene requires hStaf/ZNF143. Nucleic Acids Res. 2007;35(10):3453-64. PMID: 17478512

- Yamamoto Y, Matsuyama H, Chochi Y, Okuda M, Kawauchi S, Inoue R, Furuya T, Oga A, Naito K, Sasaki K. Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. Cancer Genet Cytogenet. 2007 Apr 1;174(1):42-7. PMID: 17350465

- Hanks S, Coleman K, Summersgill B, Messahel B, Williamson D, Pritchard-Jones K, Strefford J, Swansbury J, Plaja A, Shipley J, Rahman N. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer Lett. 2006 Aug 8;239(2):234-8. PMID: 16182441

- Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Méhes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004 Nov;36(11):1159-61. PMID: 15475955