Abstract: Described herein are methods of preventing cancer, treating cancer, inhibiting tumor growth, predicting patient outcomes, optimizing dosage, and monitoring the efficacy of treatment. In particular, certain microRNAs and messenger RNAs are useful indicators of response to NSAID chemoprevention and therapy of patients having Lynch syndrome or hereditary non-polyposis colorectal cancer.

Abstract: We have now discovered that eukaryotes, including mammals, have a DNA mismatch repair pathway analogous to the pathway that exists in bacteria. Defects or alterations in this mismatch repair pathway in a mammal, such as a human, will result in the accumulation of unstable repeated DNA sequences. Such a phenotype has a high correlation to disease state in a number of cancers, such as hereditary colon cancers. Accordingly, discovering a defect or alteration in the pathway can be diagnostic of a predisposition to cancer, and prognostic for a particular cancer. We have also discovered and sequenced one of the genes in this pathway in a number of mammals, including humans. This gene, referred to herein as MSH2, has many applications. It can be used in assays, to express gene product, for drug screens, and therapeutically. We also disclose herein a method for screening for other genes in this mismatch repair pathway.

Abstract: We have now discovered that eukaryotes, including mammals, have a DNA mismatch repair pathway analogous to the pathway that exists in bacteria. Defects or alterations in this mismatch repair pathway in a mammal, such as a human, will result in the accumulation of unstable repeated DNA sequences. Such a phenotype has a high correlation to disease state in a number of cancers, such as hereditary colon cancers. Accordingly, discovering a defect or alteration in the pathway can be diagnostic of a predisposition to cancer, and prognostic for a particular cancer.

Abstract: Retroviruses are RNA viruses that must insert a DNA copy (cDNA) of their genome into the host genome in order to carryout a productive infection. One host cellular pathway that defends against retroviral cDNA integration involves highly conserved proteins of a host DNA repair pathway. These proteins represent novel targets for anti-retroviral drugs. The invention presented herein provides, inter alia, methods of identifying compounds that induce a DNA repair pathway and/or inhibit retroviral cDNA integration into a host genome, compounds thus identified, uses of such compounds, and kits for identifying and testing of the efficacy of compounds in inducing a DNA repair pathway, inhibiting retroviral cDNA integration, and inhibiting retroviral infection.

Abstract: Compositions, and products comprising a MutS homolog which binds to a mismatched region of a duplex DNA molecule in the presence of ADP are provided, as are methods of binding MutS homologs to mismatched DNA in the presence of ADP. The use of MutL homolog derivatives in combination with MutS homologs is also included. Nonhuman mammals which are nullizygous for both Msh2 and p53 are also provided, as are methods of making and using the same.

Abstract: Compositions, and products comprising a MutS homolog which binds to a mismatched region of a duplex DNA molecule in the presence of ADP are provided, as are methods of binding MutS homologs to mismatched DNA in the presence of ADP. The use of MutL homolog derivatives in combination with MutS homologs is also included. Nonhuman mammals which are nullizygous for both Msh2 and p53 are also provided, as are methods of making and using the same.

Abstract: The invention concerns a method for the determination of the genomic instability at 5 selected microsatellite loci. The analysis of these selected loci is suitable for making prognostic tumour diagnoses, for analysing hereditary tumor predisposition as well as for early tumor detection. This method is of particular importance for the diagnosis of tumors of the gastrointestinal tract such as colorectal tumors.