title: Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability.
abstract: BACKGROUND
  Protein tyrosine phosphatases (PTPs) like their antagonizing protein tyrosine kinases are key regulators of signal transduction thereby assuring normal control of cellular growth and differentiation. Increasing evidence suggests that mutations in PTP genes are associated with human malignancies. For example, mutational analysis of the tyrosine phosphatase (PTP) gene superfamily uncovered genetic alterations in about 26% of colorectal tumors. Since in these studies tumors have not been stratified according to genetic instability status we hypothesized that colorectal tumors characterized by high-level of microsatellite instability (MSI-H) might show an increased frequency of frameshift mutations in those PTP genes that harbor long mononucleotide repeats in their coding region (cMNR).
  
  
  RESULTS
  Using bioinformatic analysis we identified 16 PTP candidate genes with long cMNRs that were examined for genetic alterations in 19 MSI-H colon cell lines, 54 MSI-H colorectal cancers, and 17 MSI-H colorectal adenomas. Frameshift mutations were identified only in 6 PTP genes, of which PTPN21 show the highest mutation frequency at all in MSI-H tumors (17%).
  
  
  CONCLUSIONS
  Although about 32% of MSI-H tumors showed at least one affected PTP gene, and cMNR mutation rates in PTPN21, PTPRS, and PTPN5 are higher than the mean mutation frequency of MNRs of the same length, mutations within PTP genes do not seem to play a common role in MSI tumorigenesis, since no cMNR mutation frequency reached statistical significance and therefore, failed prediction as a Positive Selective Target Gene.
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany. sebastian.korff@med.uni-heidelberg.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Korff
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Woerner
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yuan
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Johannes
authors.initials: J
authors.lastname: Gebert
mesh_terms: D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D016366:Open Reading Frames; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*
chemical_list: D017027:Protein Tyrosine Phosphatases