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

doi:10.1126/science.1096096

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

Istituto Oncologico Candiolo

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1164-1166
Number of pages	3
Journal	Science
Volume	304
Issue number	5674
DOIs	https://doi.org/10.1126/science.1096096
Publication status	Published - May 21 2004

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Wang, Z., Shen, D., Parsons, D. W., Bardelli, A., Sager, J., Szabo, S., Ptak, J., Silliman, N., Peters, B. A., Van Der Heidjden, M. S., Parmigiani, G., Yan, H., Wang, T. L., Riggins, G., Powell, S. M., Willson, J. K. V., Markowitz, S., Kinzler, K. W., Vogelstein, B., & 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

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

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title = "Mutational analysis of the tyrosine phosphatome in colorectal cancers",

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.",

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

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AU - Ptak, Janine

AU - Silliman, Natalie

AU - Peters, Brock A.

AU - Van Der Heidjden, Michiel S.

AU - Parmigiani, Geovanni

AU - Yan, Hai

AU - Wang, Tian Li

AU - Riggins, Greg

AU - Powell, Stevan M.

AU - Willson, James K V

AU - Markowitz, Sanford

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Velculescu, Victor E.

PY - 2004/5/21

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N2 - 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.

AB - 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.

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Mutational analysis of the tyrosine phosphatome in colorectal cancers

Abstract

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