Abstract
The MBD4 gene is involved in the repair of mutation at methyl-CpG dinucleotides. In microsatellite unstable tumours MBD4 can itself be mutated at an exonic polynucleotide tract. By analysing DNA from microdissected tumour samples we have found that both frequency and pattern of mutation are more significant than originally reported. © 2000 Cancer Research Campaign http://www.bjcancer.com
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Abdel-Rahman WM, Georgiades IB, Curtis LJ, Arends MJ and Wyllie AH (1999) Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis. Oncogene 18: 2139–2142
Bader S, Walker M, Hendrich B, Bird A, Bird C, Hooper M and Wyllie A (1999) Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency. Oncogene 18: 8044–8047
Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, Golemis EA, Genuardi M and Neri G (1999) MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proc Natl Acad Sci USA 96: 3969–3974
Bubb VJ, Curtis LJ, Cunningham C, Dunlop MG, Carothers AD, Morris RG, White S, Bird CC and Wyllie AH (1996) Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer. Oncogene 12: 2641–2649
Chung Y-J, Kim K-M, Choi J-R, Choi S-W and Rhyu M-G (1999) Relationship between intratumoral histological heterogeneity and genetic abnormalities in gastric carcinoma with microsatellite instability. Int J Cancer 82: 782–788
Hendrich B and Bird A (1998) Identification and characterisation of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18: 6538–6547
Hendrich B, Hardeland U, Ng H-H, Jiricny J and Bird A (1999) The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature 401: 301–304
Markowitz S, Wang J, Myeroff L, Parsons R, Sun LZ, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M and Willson JKV (1995) Inactivation of the Type II TGFβ receptor in colon cancer cells with microsatellite instability. Science 268: 1336–1338
Riccio A, Aaltonen LA, Godwin AK, Loukola A, Percesepe A, Salovaara R, Masciullo V, Genuardi M, Paravatou-Petsotas M, Bassi DE, Ruggeri BA, Klein-Szanto AJP, Testa JR, Neri G and Bellacosa A (1999) The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nature Genet 23: 266–268
Samowitz WS and Slattery ML (1999) Regional reproducibility of microsatellite instability in sporadic colorectal cancer. Genes Chromos & Cancer 26: 106–114
Sankila R, Aaltonen LA, Jarvinen HJ and Mecklin JP (1996) Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 110: 682–687
Souza RF, Appel R, Yin J, Wang S, Smolinksi KN, Abraham JM, Zou T-T, Shi Y-Q, Lei J, Cottrel J, Cymes K, Biden K, Simms L, Leggett B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J and Meltzer SJ (1996) Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nature Genet 14: 255–257
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Bader, S., Walker, M. & Harrison, D. Most microsatellite unstable sporadic colorectal carcinomas carry MBD4 mutations. Br J Cancer 83, 1646–1649 (2000). https://doi.org/10.1054/bjoc.2000.1482
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1482
Keywords
This article is cited by
-
A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells
British Journal of Cancer (2007)
-
MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR
Oncogene (2004)
-
MBD4 deficiency reduces the apoptotic response to DNA-damaging agents in the murine small intestine
Oncogene (2003)
-
Methyl-CpG binding proteins and cancer: are MeCpGs more important than MBDs?
Oncogene (2002)