Mutational analysis of the tyrosine phosphatome in colorectal cancers

Zhenghe Wang, Dong Shen, D. Williams Parsons, Alberto Bardelli, Jason Sager, Steve Szabo, Janine Ptak, Natalie Silliman, Brock A. Peters, Michiel S. Van Der Heidjden, Geovanni Parmigiani, Hai Yan, Tian Li Wang, Greg Riggins, Stevan M. Powell, James K V Willson, Sanford Markowitz, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu

Research output: Contribution to journalArticle

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Abstract

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.

Original languageEnglish
Pages (from-to)1164-1166
Number of pages3
JournalScience
Volume304
Issue number5674
DOIs
Publication statusPublished - May 21 2004

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Protein Tyrosine Phosphatases
Phosphoric Monoester Hydrolases
Tyrosine
Colorectal Neoplasms
Nonsense Codon
Phosphoprotein Phosphatases
Missense Mutation
Tumor Suppressor Genes
Protein-Tyrosine Kinases
Stomach Neoplasms
Lung Neoplasms
Neoplasms
Carcinogenesis
Phosphorylation
Breast Neoplasms
Mutation
Growth
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Wang, Z., Shen, D., Parsons, D. W., Bardelli, A., Sager, J., Szabo, S., ... Velculescu, V. E. (2004). Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science, 304(5674), 1164-1166. https://doi.org/10.1126/science.1096096

Mutational analysis of the tyrosine phosphatome in colorectal cancers. / Wang, Zhenghe; Shen, Dong; Parsons, D. Williams; Bardelli, Alberto; Sager, Jason; Szabo, Steve; Ptak, Janine; Silliman, Natalie; Peters, Brock A.; Van Der Heidjden, Michiel S.; Parmigiani, Geovanni; Yan, Hai; Wang, Tian Li; Riggins, Greg; Powell, Stevan M.; Willson, James K V; Markowitz, Sanford; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.

In: Science, Vol. 304, No. 5674, 21.05.2004, p. 1164-1166.

Research output: Contribution to journalArticle

Wang, Z, Shen, D, Parsons, DW, Bardelli, A, Sager, J, Szabo, S, Ptak, J, Silliman, N, Peters, BA, Van Der Heidjden, MS, Parmigiani, G, Yan, H, Wang, TL, Riggins, G, Powell, SM, Willson, JKV, Markowitz, S, Kinzler, KW, Vogelstein, B & Velculescu, VE 2004, 'Mutational analysis of the tyrosine phosphatome in colorectal cancers', Science, vol. 304, no. 5674, pp. 1164-1166. https://doi.org/10.1126/science.1096096
Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S et al. Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science. 2004 May 21;304(5674):1164-1166. https://doi.org/10.1126/science.1096096
Wang, Zhenghe ; Shen, Dong ; Parsons, D. Williams ; Bardelli, Alberto ; Sager, Jason ; Szabo, Steve ; Ptak, Janine ; Silliman, Natalie ; Peters, Brock A. ; Van Der Heidjden, Michiel S. ; Parmigiani, Geovanni ; Yan, Hai ; Wang, Tian Li ; Riggins, Greg ; Powell, Stevan M. ; Willson, James K V ; Markowitz, Sanford ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Velculescu, Victor E. / Mutational analysis of the tyrosine phosphatome in colorectal cancers. In: Science. 2004 ; Vol. 304, No. 5674. pp. 1164-1166.
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