ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor

Abstract Inflammatory myofibroblastic tumors are rare mesenchymal neoplasms frequently harboring oncogenic chromosomal rearrangements, most commonly, involving the ALK (anaplastic lymphoma kinase) gene. Treatment of this molecularly defined subgroup with the anaplastic lymphoma kinase inhibitor criz...

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Autores principales:	Sebastian Y. F. Michels, Andreas H. Scheel, Thomas Wündisch, Johannes M. Heuckmann, Roopika Menon, Michael Puesken, Carsten Kobe, Helen Pasternack, Carina Heydt, Matthias Scheffler, Rieke Fischer, Anne M. Schultheis, Sabine Merkelbach-Bruse, Lukas Heukamp, Reinhard Büttner, Jürgen Wolf
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/33a80232e38044a3a05d9a9bbd74b52a
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spelling	oai:doaj.org-article:33a80232e38044a3a05d9a9bbd74b52a2021-12-02T14:18:34ZALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor10.1038/s41698-017-0004-32397-768Xhttps://doaj.org/article/33a80232e38044a3a05d9a9bbd74b52a2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-017-0004-3https://doaj.org/toc/2397-768XAbstract Inflammatory myofibroblastic tumors are rare mesenchymal neoplasms frequently harboring oncogenic chromosomal rearrangements, most commonly, involving the ALK (anaplastic lymphoma kinase) gene. Treatment of this molecularly defined subgroup with the anaplastic lymphoma kinase inhibitor crizotinib has shown to be effective. However, comparable to lung adenocarcinoma, resistance inevitably develops. Second generation anaplastic lymphoma kinase inhibitors such as ceritinib are able to overcome acquired resistance to crizotinib. Here, we report the case of a patient with an inflammatory myofibroblastic tumors harboring a DCTN1-ALK fusion who developed resistance to crizotinib treatment. Next-generation sequencing of a rebiopsy sample revealed the acquisition of the ALK G1269A mutation as a mechanism of resistance. Therapy with ceritinib resulted in a short but profound clinical, metabolic and morphologic response. This case illustrates that (i) different tumor entities may share similar oncogenic driver mechanisms, rendering them vulnerable for the same therapeutic substances and (ii) likewise, the same mode of resistance may occur under targeted therapy among different tumor entities.Sebastian Y. F. MichelsAndreas H. ScheelThomas WündischJohannes M. HeuckmannRoopika MenonMichael PueskenCarsten KobeHelen PasternackCarina HeydtMatthias SchefflerRieke FischerAnne M. SchultheisSabine Merkelbach-BruseLukas HeukampReinhard BüttnerJürgen WolfNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 1, Iss 1, Pp 1-4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sebastian Y. F. Michels Andreas H. Scheel Thomas Wündisch Johannes M. Heuckmann Roopika Menon Michael Puesken Carsten Kobe Helen Pasternack Carina Heydt Matthias Scheffler Rieke Fischer Anne M. Schultheis Sabine Merkelbach-Bruse Lukas Heukamp Reinhard Büttner Jürgen Wolf ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
description	Abstract Inflammatory myofibroblastic tumors are rare mesenchymal neoplasms frequently harboring oncogenic chromosomal rearrangements, most commonly, involving the ALK (anaplastic lymphoma kinase) gene. Treatment of this molecularly defined subgroup with the anaplastic lymphoma kinase inhibitor crizotinib has shown to be effective. However, comparable to lung adenocarcinoma, resistance inevitably develops. Second generation anaplastic lymphoma kinase inhibitors such as ceritinib are able to overcome acquired resistance to crizotinib. Here, we report the case of a patient with an inflammatory myofibroblastic tumors harboring a DCTN1-ALK fusion who developed resistance to crizotinib treatment. Next-generation sequencing of a rebiopsy sample revealed the acquisition of the ALK G1269A mutation as a mechanism of resistance. Therapy with ceritinib resulted in a short but profound clinical, metabolic and morphologic response. This case illustrates that (i) different tumor entities may share similar oncogenic driver mechanisms, rendering them vulnerable for the same therapeutic substances and (ii) likewise, the same mode of resistance may occur under targeted therapy among different tumor entities.
format	article
author	Sebastian Y. F. Michels Andreas H. Scheel Thomas Wündisch Johannes M. Heuckmann Roopika Menon Michael Puesken Carsten Kobe Helen Pasternack Carina Heydt Matthias Scheffler Rieke Fischer Anne M. Schultheis Sabine Merkelbach-Bruse Lukas Heukamp Reinhard Büttner Jürgen Wolf
author_facet	Sebastian Y. F. Michels Andreas H. Scheel Thomas Wündisch Johannes M. Heuckmann Roopika Menon Michael Puesken Carsten Kobe Helen Pasternack Carina Heydt Matthias Scheffler Rieke Fischer Anne M. Schultheis Sabine Merkelbach-Bruse Lukas Heukamp Reinhard Büttner Jürgen Wolf
author_sort	Sebastian Y. F. Michels
title	ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
title_short	ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
title_full	ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
title_fullStr	ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
title_full_unstemmed	ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
title_sort	alk g1269a mutation as a potential mechanism of acquired resistance to crizotinib in an alk-rearranged inflammatory myofibroblastic tumor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/33a80232e38044a3a05d9a9bbd74b52a
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ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor

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