Journal ArticleDOI
MSH2 deficient mice are viable and susceptible to lymphoid tumours.
Armin Reitmair,Rudolf Schmits,A. Ewel,Bharati Bapat,Mark Redston,Angela Mitri,Paul Waterhouse,Hans-Willi Mittrücker,Andrew Wakeham,B. Liu,A. Thomason,Henrik Griesser,Steve Gallinger,W.G. Ballhausen,Richard Fishel,T. W. Mak +15 more
TLDR
A direct link between MSH2 deficiency and the pathogenesis of cancer is established and these mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti–cancer agents.Abstract:
Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.read more
Citations
More filters
sources and effects of ionizing radiation
TL;DR: This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices, in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation.
Journal ArticleDOI
Rates of Spontaneous Mutation
TL;DR: It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates in broad groups of organisms.
Journal ArticleDOI
Microsatellite Instability in Colorectal Cancer
C. Richard Boland,Ajay Goel +1 more
TL;DR: Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance, and do not have the same response to chemotherapeutics.
Journal ArticleDOI
Mechanisms and functions of DNA mismatch repair
TL;DR: Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
Journal ArticleDOI
Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.
Sean M. Baker,Annemieke W. Plug,Prolla Ta,Bronner Ce,A. C. Harris,Xiang Yao,Christie Dm,Monell C,Norman Arnheim,Allan Bradley,Terry Ashley,R. M. Liskay +11 more
TL;DR: Findings suggest that Mlh1 is involved in DNA mismatch repair and meiotic crossing over in mice deficient in another mismatch repair gene, M lh1.
References
More filters
Journal ArticleDOI
Microsatellite instability in cancer of the proximal colon
TL;DR: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q, and this instability was significantly correlated with the tumor's location in the proximal colon and with increased patient survival and loss of heterozygosity.
Journal ArticleDOI
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
Richard Fishel,Mary Kay Lescoe,M.R.S. Rao,Neal G. Copeland,Nancy A. Jenkins,Judy Garber,Michael F. Kane,Richard D. Kolodner +7 more
TL;DR: Data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with H NPCC suggest that hMSH2 is the HNPCC gene.
Journal ArticleDOI
Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis
TL;DR: It is shown that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA . dT) sequences and other simple repeats, and it is concluded that these mutations reflect a previously undescribed form of carcinogenesis in the colon mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation').
Journal ArticleDOI
Clues to the pathogenesis of familial colorectal cancer
Lauri A. Aaltonen,Päivi Peltomäki,Fredrick S. Leach,Pertti Sistonen,Lea Pylkkänen,Jukka-Pekka Mecklin,Heikki Järvinen,Steven M. Powell,Jin Jen,Stanley R. Hamilton,Gloria M. Petersen,Kenneth W. Kinzler,Bert Vogelstein,Albert de la Chapelle +13 more
TL;DR: Molecular features of "familial" cancers were compared with those of sporadic colon cancers, and a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes is suggested.
Journal ArticleDOI
Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
Kirk R. Thomas,Mario R. Capecchi +1 more
TL;DR: This work mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells and compared the gene-targeting efficiencies of two classes of neor-Hprt recombinant vectors.
Related Papers (5)
Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
Fredrick S. Leach,Nicholas C. Nicolaides,Nickolas Papadopoulos,Bo Liu,Jin Jen,Ramon Parsons,Päivi Peltomäki,Pertti Sistonen,Lauri A. Aaltonen,Minna Nyström-Lahti,Xin Yuan Guan,Ji Zhang,Paul S. Meltzer,Jing Wei Yu,Fa Ten Kao,David J. Chen,Karen M. Cerosaletti,R. E. Keith Fournier,Sean Todd,Tracey B. Lewis,Robin J. Leach,Susan L. Naylor,Jean Weissenbach,Jukka-Pekka Mecklin,Heikki Järvinen,Gloria M. Petersen,Stanley R. Hamilton,Jane Green,Jeremy R. Jass,Patrice Watson,Henry T. Lynch,Jeffrey M. Trent,Albert de la Chapelle,Kenneth W. Kinzler,Bert Vogelstein +34 more
Mutation of a mutL homolog in hereditary colon cancer
Nickolas Papadopoulos,Nicholas C. Nicolaides,Ying Fei Wei,Steven M. Ruben,Kenneth C. Carter,Craig A. Rosen,William A. Haseltine,Robert D. Fleischmann,Claire M. Fraser,Mark Raymond Adams,J. Craig Venter,Stanley R. Hamilton,Gloria M. Petersen,Patrice Watson,Henry T. Lynch,Päivi Peltomäki,Jukka-Pekka Mecklin,Albert de la Chapelle,Kenneth W. Kinzler,Bert Vogelstein +19 more
Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.
Nicholas C. Nicolaides,Nickolas Papadopoulos,Bo Liu,Ying Fei Weit,Kenneth C. Carter,Steven M. Ruben,Craig A. Rosen,William A. Haseltine,Robert D. Fleischmann,Claire M. Fraser,Mark Raymond Adams,J. Craig Venter,Malcolm G. Dunlop,Stanley R. Hamilton,Gloria M. Petersen,Albert de la Chapelle,Bert Vogelstein,Kenneth W. Kinzler +17 more