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 journalArticlepeer-review

405 Scopus citations

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 (US)
Pages (from-to)1164-1166
Number of pages3
JournalScience
Volume304
Issue number5674
DOIs
StatePublished - May 21 2004

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Mutational analysis of the tyrosine phosphatome in colorectal cancers'. Together they form a unique fingerprint.

Cite this