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Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability.
BMC Cancer. 2008 Nov 10; 8:329.BC

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%).

CONCLUSION

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+Show Affiliations

Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany. sebastian.korff@med.uni-heidelberg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19000305

Citation

Korff, Sebastian, et al. "Frameshift Mutations in Coding Repeats of Protein Tyrosine Phosphatase Genes in Colorectal Tumors With Microsatellite Instability." BMC Cancer, vol. 8, 2008, p. 329.
Korff S, Woerner SM, Yuan YP, et al. Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability. BMC Cancer. 2008;8:329.
Korff, S., Woerner, S. M., Yuan, Y. P., Bork, P., von Knebel Doeberitz, M., & Gebert, J. (2008). Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability. BMC Cancer, 8, 329. https://doi.org/10.1186/1471-2407-8-329
Korff S, et al. Frameshift Mutations in Coding Repeats of Protein Tyrosine Phosphatase Genes in Colorectal Tumors With Microsatellite Instability. BMC Cancer. 2008 Nov 10;8:329. PubMed PMID: 19000305.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability. AU - Korff,Sebastian, AU - Woerner,Stefan M, AU - Yuan,Yan P, AU - Bork,Peer, AU - von Knebel Doeberitz,Magnus, AU - Gebert,Johannes, Y1 - 2008/11/10/ PY - 2007/11/20/received PY - 2008/11/10/accepted PY - 2008/11/13/pubmed PY - 2009/7/1/medline PY - 2008/11/13/entrez SP - 329 EP - 329 JF - BMC cancer JO - BMC Cancer VL - 8 N2 - 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%). CONCLUSION: 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. SN - 1471-2407 UR - https://www.unboundmedicine.com/medline/citation/19000305/Frameshift_mutations_in_coding_repeats_of_protein_tyrosine_phosphatase_genes_in_colorectal_tumors_with_microsatellite_instability_ L2 - https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-329 DB - PRIME DP - Unbound Medicine ER -