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Mutational and functional analysis of the tyrosine phosphatase gene family in melanoma

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center




  • V Walia
  • SA Rosenberg
  • RC Elble
  • T Waldman
  • Y Samuels


To determine the role of novel phosphatase genes that regulate growth signaling in melanoma-genesis, we performed a mutational analysis of tyrosine phosphatase gene family in 80 human malignant melanoma samples. We found 23 phosphatase genes frequently mutated in melanoma and focused on receptor protein tyrosine phosphatase, receptor type D (PTPRD). Our lab previously reported 10 nonsynonymous mutations in PTPRD in 7/57 melanoma samples (Solomon, 2008). To complement this, we now report a total of 17 somatic mutations in PTPRD in 15/80 samples indicating that PTPRD is mutated in 18.75% of melanomas. To understand the function of PTPRD, we screened its interacting partners by creating a tet-regulated, flag-tagged wild-type and D1521A mutant of PTPRD, based on its homology to well-characterized D1074A mutant of PTPRT having impaired phosphatase activity but unaltered substrate-affinity (Zhang, 2007). Using mass spectrometry, we characterized interacting partners of PTPRD and validated two of its novel binding partners by co-immunoprecipitation. Identification of PTPRD partners might reveal PTPRD-regulated substrates that could be the novel targets in tumors bearing genetically mutant PTPRD. Since PTPRD is mutated in glioblastomas, adenocarcinoma of the colon and lung, our mechanistic data, might, therefore be of value for a large number of human cancers.

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