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A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions
The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-t...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381411/ https://www.ncbi.nlm.nih.gov/pubmed/35858593 http://dx.doi.org/10.1016/j.xcrm.2022.100686 |
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author | Estrada-Zuniga, Cynthia M. Cheng, Zi-Ming Ethiraj, Purushoth Guo, Qianjin Gonzalez-Cantú, Hector Adderley, Elaina Lopez, Hector Landry, Bethany N. Zainal, Abir Aronin, Neil Ding, Yanli Wang, Xiaojing Aguiar, Ricardo C.T. Dahia, Patricia L.M. |
author_facet | Estrada-Zuniga, Cynthia M. Cheng, Zi-Ming Ethiraj, Purushoth Guo, Qianjin Gonzalez-Cantú, Hector Adderley, Elaina Lopez, Hector Landry, Bethany N. Zainal, Abir Aronin, Neil Ding, Yanli Wang, Xiaojing Aguiar, Ricardo C.T. Dahia, Patricia L.M. |
author_sort | Estrada-Zuniga, Cynthia M. |
collection | PubMed |
description | The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy. |
format | Online Article Text |
id | pubmed-9381411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-93814112022-08-18 A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions Estrada-Zuniga, Cynthia M. Cheng, Zi-Ming Ethiraj, Purushoth Guo, Qianjin Gonzalez-Cantú, Hector Adderley, Elaina Lopez, Hector Landry, Bethany N. Zainal, Abir Aronin, Neil Ding, Yanli Wang, Xiaojing Aguiar, Ricardo C.T. Dahia, Patricia L.M. Cell Rep Med Report The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy. Elsevier 2022-07-19 /pmc/articles/PMC9381411/ /pubmed/35858593 http://dx.doi.org/10.1016/j.xcrm.2022.100686 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Estrada-Zuniga, Cynthia M. Cheng, Zi-Ming Ethiraj, Purushoth Guo, Qianjin Gonzalez-Cantú, Hector Adderley, Elaina Lopez, Hector Landry, Bethany N. Zainal, Abir Aronin, Neil Ding, Yanli Wang, Xiaojing Aguiar, Ricardo C.T. Dahia, Patricia L.M. A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title | A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title_full | A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title_fullStr | A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title_full_unstemmed | A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title_short | A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions |
title_sort | ret::grb2 fusion in pheochromocytoma defies the classic paradigm of ret oncogenic fusions |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381411/ https://www.ncbi.nlm.nih.gov/pubmed/35858593 http://dx.doi.org/10.1016/j.xcrm.2022.100686 |
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