Global assessment of the protein tyrosine phosphatome in cancer

Tonks, N., Lucito, R. (October 2014) Global assessment of the protein tyrosine phosphatome in cancer. Cancer Research, 74 (19). ISSN 0008-5472

URL: http://cancerres.aacrjournals.org/content/74/19_Su...
DOI: 10.1158/1538-7445.am2014-4178

Abstract

Receptor tyrosine kinases and non-receptor tyrosine kinases are an important class of molecules controlling a large number of processes from growth to metabolic regulation. These tyrosine kinases have been well studied and scrutinized for their role in these normal processes as well as abnormal processes, such as cancer. Parallel to these kinases are more that 100 tyrosine phosphatases, which also fall into either receptor or non receptor classifications. While some of these phosphatases antagonize the tyrosine kinases others including many of the receptor bound phosphatases are critical in their own right in signaling processes such as pro survival, proliferation, etc. Although tyrosine kinases have been well studied, the study of tyrosine phosphatases has lagged. Numerous tyrosine phosphatases have been identified that are misregulated and important for cancer growth including PTPRD in breast cancer, and PTPRZ1 in small cell lung cancer as well as many others. However there has been no comprehensive study of all PTPs or the protein tyrosine phosphatome (PTPome), to identify which have a role in cancer. We as a cancer community are fortunate to have access to such a wide array of data types from a number of data sources such as TCGA, where we can determine if the PTPs are mis regulated in more than 20 types of cancers. We used TCGA data for all tumor types and subsetted the data to analyze the PTPome for all data types including expression, methylation, copy number and sequence data where available. Thus far we have identified known PTPs involved in a number of cancers, including PTPRD and PTPRZ1, but have also identified a number of PTPs altered in cancers that were less characterized such as the alteration of PTPRD in melanoma which is predominantly by mutations with much fewer deletions. While many of these mutations are missense and are difficult to characterize there are also a number of non-sense mutations, which would severely alter function as well as a number of splice site mutation of which some severely alter function and others are likely to alter function. The identification of this PTP is but one example to demonstrate the richness of this dataset. This analysis has been extremely useful to identify the PTPs that are altered in cancer and these results will be useful to many in the research community that are interested in PTP involvement in cancer but will also be of even greater use to those researchers who have not appreciated the vast importance of these under studied proteins.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: diseases & disorders > cancer
Publication Type > Meeting Abstract
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: Matt Covey
Date: 1 October 2014
Date Deposited: 29 May 2015 20:00
Last Modified: 06 Feb 2018 21:44
URI: http://repository.cshl.edu/id/eprint/31549

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