Universität zu Köln

Michels, Sebastian Y. F., Scheel, Andreas H., Wuendisch, Thomas, Heuckmann, Johannes M., Menon, Roopika, Puesken, Michael, Kobe, Carsten, Pasternack, Helen, Heydt, Carina, Scheffler, Matthias, Fischer, Rieke, Schultheis, Anne M., Merkelbach-Bruse, Sabine, Heukamp, Lukas ORCID: 0000-0002-3388-3482, Buettner, Reinhard and Woelf, Jurgen (2017). ALK(G1269A) mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor. npj Precis. Oncol., 1. LONDON: NATURE PUBLISHING GROUP. ISSN 2397-768X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Michels, Sebastian Y. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheel, Andreas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuendisch, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Heuckmann, Johannes M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Menon, Roopika UNSPECIFIED UNSPECIFIED UNSPECIFIED Puesken, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kobe, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasternack, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheffler, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Rieke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultheis, Anne M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas UNSPECIFIED orcid.org/0000-0002-3388-3482 UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Woelf, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236440
DOI:	10.1038/s41698-017-0004-3
Journal or Publication Title:	npj Precis. Oncol.
Volume:	1
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2397-768X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INHIBITOR; KINASE Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23644