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JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations

Cancer-associated protein tyrosine kinase (PTK) mutations usually are gain-of-function (GOF) mutations that drive tumor growth and metastasis. We have found 50 JAK1 truncating mutations in 36 of 635 gynecologic tumors in the Total Cancer Care® (TCC®) tumor bank. Among cancer cell lines containing JA...

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Detalles Bibliográficos
Autores principales: Ren, Yuan, Zhang, Yonghong, Liu, Richard Z., Fenstermacher, David A., Wright, Kenneth L., Teer, Jamie K., Wu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807107/
https://www.ncbi.nlm.nih.gov/pubmed/24154688
http://dx.doi.org/10.1038/srep03042
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author Ren, Yuan
Zhang, Yonghong
Liu, Richard Z.
Fenstermacher, David A.
Wright, Kenneth L.
Teer, Jamie K.
Wu, Jie
author_facet Ren, Yuan
Zhang, Yonghong
Liu, Richard Z.
Fenstermacher, David A.
Wright, Kenneth L.
Teer, Jamie K.
Wu, Jie
author_sort Ren, Yuan
collection PubMed
description Cancer-associated protein tyrosine kinase (PTK) mutations usually are gain-of-function (GOF) mutations that drive tumor growth and metastasis. We have found 50 JAK1 truncating mutations in 36 of 635 gynecologic tumors in the Total Cancer Care® (TCC®) tumor bank. Among cancer cell lines containing JAK1 truncating mutations in the Cancer Cell Line Encyclopedia databank, 68% are gynecologic cancer cells. Within JAK1 the K142, P430, and K860 frame-shift mutations were identified as hot spot mutation sites. Sanger sequencing of cancer cell lines, primary tumors, and matched normal tissues confirmed the JAK1 mutations and showed that these mutations are somatic. JAK1 mediates interferon (IFN)-γ-regulated tumor immune surveillance. Functional assays show that JAK1 deficient cancer cells are defective in IFN-γ-induced LMP2 and TAP1 expression, loss of which inhibits presentation of tumor antigens. These findings identify recurrent JAK1 truncating mutations that could contribute to tumor immune evasion in gynecologic cancers, especially in endometrial cancer.
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spelling pubmed-38071072013-10-24 JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations Ren, Yuan Zhang, Yonghong Liu, Richard Z. Fenstermacher, David A. Wright, Kenneth L. Teer, Jamie K. Wu, Jie Sci Rep Article Cancer-associated protein tyrosine kinase (PTK) mutations usually are gain-of-function (GOF) mutations that drive tumor growth and metastasis. We have found 50 JAK1 truncating mutations in 36 of 635 gynecologic tumors in the Total Cancer Care® (TCC®) tumor bank. Among cancer cell lines containing JAK1 truncating mutations in the Cancer Cell Line Encyclopedia databank, 68% are gynecologic cancer cells. Within JAK1 the K142, P430, and K860 frame-shift mutations were identified as hot spot mutation sites. Sanger sequencing of cancer cell lines, primary tumors, and matched normal tissues confirmed the JAK1 mutations and showed that these mutations are somatic. JAK1 mediates interferon (IFN)-γ-regulated tumor immune surveillance. Functional assays show that JAK1 deficient cancer cells are defective in IFN-γ-induced LMP2 and TAP1 expression, loss of which inhibits presentation of tumor antigens. These findings identify recurrent JAK1 truncating mutations that could contribute to tumor immune evasion in gynecologic cancers, especially in endometrial cancer. Nature Publishing Group 2013-10-24 /pmc/articles/PMC3807107/ /pubmed/24154688 http://dx.doi.org/10.1038/srep03042 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Ren, Yuan
Zhang, Yonghong
Liu, Richard Z.
Fenstermacher, David A.
Wright, Kenneth L.
Teer, Jamie K.
Wu, Jie
JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title_full JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title_fullStr JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title_full_unstemmed JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title_short JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
title_sort jak1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807107/
https://www.ncbi.nlm.nih.gov/pubmed/24154688
http://dx.doi.org/10.1038/srep03042
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