Tumors of DNA mismatch repair-deficient hosts exhibit dramatic increases in genomic instability
AUTOR(ES)
Baross-Francis, Agnes
FONTE
The National Academy of Sciences
RESUMO
DNA mismatch repair (MMR) deficiency is associated with an increased mutational burden and predisposition to certain malignancies. Relatively little is known, however, about gene-specific mutation frequencies within MMR-deficient primary tumors. Thymic lymphomas from Msh2−/− mice were thus analyzed by using a lacI-based transgenic shuttle-phage mutation detection system. All tumors exhibited greatly elevated lacI gene mutation frequencies, ranging from 3.2- to 17.4-fold above the ≈15-fold elevations present within normal Msh2−/− thymi. In addition, lacI genes harboring multiple changes, including clusters of mutations, were found in thymic tumor DNA. The results suggest that an additional mutator activity, such as an error-prone DNA polymerase, leads to increased genomic instability in these MMR-deficient tumors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21146Documentos Relacionados
- CTG repeat instability and size variation timing in DNA repair-deficient mice
- Human MRE11 is inactivated in mismatch repair-deficient cancers
- The Oxidized Deoxynucleoside Triphosphate Pool Is a Significant Contributor to Genetic Instability in Mismatch Repair-Deficient Cells
- Altered spectra of hypermutation in DNA repair-deficient mice.
- Apurinic DNA endonuclease activities in repair-deficient human cell lines.