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Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications
Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, w...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757245/ https://www.ncbi.nlm.nih.gov/pubmed/23800680 |
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author | Jiang, Yunyun Janku, Filip Subbiah, Vivek Angelo, Laura S. Naing, Aung Anderson, Peter M. Herzog, Cynthia E. Fu, Siqing Benjamin, Robert S. Kurzrock, Razelle |
author_facet | Jiang, Yunyun Janku, Filip Subbiah, Vivek Angelo, Laura S. Naing, Aung Anderson, Peter M. Herzog, Cynthia E. Fu, Siqing Benjamin, Robert S. Kurzrock, Razelle |
author_sort | Jiang, Yunyun |
collection | PubMed |
description | Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, while somatic mutations in PTPRD have been reported in diverse tumors, germline mutations of PTPRD have not been investigated in Ewing sarcoma or other cancers. We identified a novel germline mutation in the PTPRD gene in three of eight patients (37.5%) with metastatic Ewing sarcoma. Although the functional impact in two of the patients is unclear, in one of them the aberration was annotated as a W775stop germline mutation, and would be expected to lead to gene truncation and, hence, loss of the STAT3 dephosphorylation function of PTPRD. Since STAT3 is phosphorylated after being recruited to the insulin growth factor receptor (IGF-1R), suppression of IGF-1R could attenuate the enhanced STAT3 activation expected in the presence of PTPRD mutations. Of interest, two of three patients with germline PTPRD mutations achieved durable complete responses following treatment with IGF-1R monoclonal antibody-based therapies. Our pilot data suggest that PTPRD germline mutations may play a role in the development of Ewing sarcoma, a disease of young people, and their presence may have implications for therapy. |
format | Online Article Text |
id | pubmed-3757245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-37572452013-09-03 Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications Jiang, Yunyun Janku, Filip Subbiah, Vivek Angelo, Laura S. Naing, Aung Anderson, Peter M. Herzog, Cynthia E. Fu, Siqing Benjamin, Robert S. Kurzrock, Razelle Oncotarget Research Papers Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, while somatic mutations in PTPRD have been reported in diverse tumors, germline mutations of PTPRD have not been investigated in Ewing sarcoma or other cancers. We identified a novel germline mutation in the PTPRD gene in three of eight patients (37.5%) with metastatic Ewing sarcoma. Although the functional impact in two of the patients is unclear, in one of them the aberration was annotated as a W775stop germline mutation, and would be expected to lead to gene truncation and, hence, loss of the STAT3 dephosphorylation function of PTPRD. Since STAT3 is phosphorylated after being recruited to the insulin growth factor receptor (IGF-1R), suppression of IGF-1R could attenuate the enhanced STAT3 activation expected in the presence of PTPRD mutations. Of interest, two of three patients with germline PTPRD mutations achieved durable complete responses following treatment with IGF-1R monoclonal antibody-based therapies. Our pilot data suggest that PTPRD germline mutations may play a role in the development of Ewing sarcoma, a disease of young people, and their presence may have implications for therapy. Impact Journals LLC 2013-06-05 /pmc/articles/PMC3757245/ /pubmed/23800680 Text en Copyright: © 2013 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Papers Jiang, Yunyun Janku, Filip Subbiah, Vivek Angelo, Laura S. Naing, Aung Anderson, Peter M. Herzog, Cynthia E. Fu, Siqing Benjamin, Robert S. Kurzrock, Razelle Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title | Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title_full | Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title_fullStr | Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title_full_unstemmed | Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title_short | Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications |
title_sort | germline ptprd mutations in ewing sarcoma: biologic and clinical implications |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757245/ https://www.ncbi.nlm.nih.gov/pubmed/23800680 |
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