Methods of making hypermutable cells using PMSR homologs

A method of making a mutation in a gene of interest comprising introducing into a cell containing a gene of interest a PMS2 homolog comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:23, thereby making said cell hypermutable, and selecting a mutant cell comprising a mutation in said gene of interest.

A method of generating a library of mutant genes in a cell type comprising introducing into said cell type a PMS2 homolog comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:23, thereby making hypermutable cells, wherein said PMS2 homolog is other than PMSR2 and PMSR3, incubating said hypermutable cells type to allow mutations to accumulate, extracting nucleic acid from said hypermutable cells and creating a nucleic acid library.

A method of assaying cells to detect neoplasia comprising contacting said sample with a nucleotide sequence encoding the amino acid sequence of SEQ ID NO:23 to detect expression of a polynucleotide encoding a PMS2 homolog comprising the amino acid sequence of SEQ ID NO:23, wherein expression of said PMS2 homolog is associated with neoplasia.

A method of assaying cells to detect neoplasia comprising contacting said sample with an antibody directed against a PMS2 homolog or peptide fragments thereof;

• and detecting the presence of an antibody-complex formed with the PMS2 homolog or peptide fragment thereof, thereby detecting the presence of said PMS2 homolog in said sample, wherein the presence of said PMS2 homolog is associated with neoplasia.

A method of treating a patient with cancer comprising identifying a patient with a PMS2 homolog-associated neoplasm, administering to said patient an inhibitor of expression of said PMS2 homolog wherein said inhibitor suppresses expression of said PMS2 homolog in said PMS2 homolog associated neoplasm.