Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23057
Title: Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion.
Austin Authors: McEvoy, Christopher R;Xu, Huiling;Smith, Kortnye;Etemadmoghadam, Dariush;San Leong, Huei;Choong, David Y;Byrne, David J;Iravani, Amir;Beck, Sophie;Mileshkin, Linda;Tothill, Richard W;Bowtell, David D;Bates, Bindi M;Nastevski, Violeta;Browning, Judy;Bell, Anthony H;Khoo, Chloe;Desai, Jayesh;Fellowes, Andrew P;Fox, Stephen B;Prall, Owen Wj
Affiliation: Department of Surgery, Royal Melbourne Hospital, Parkville, Australia
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia
Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia
Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
Department of Surgery, St Vincent's Hospital, Fitzroy, Australia
Austin Health Clinical School, The University of Melbourne, Heidelberg, Victoria, Australia
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia
Clinical Pathology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Issue Date: 1-May-2019
metadata.dc.date: 2019-05-01
Publication information: The Journal of clinical investigation 2019; 129(5): 1940-1945
Abstract: BRAF and CRAF are critical components of the MAPK signaling pathway which is activated in many cancer types. In approximately 1% of melanomas, BRAF or CRAF are activated through structural arrangements. We describe here a metastatic melanoma with a GOLGA4-RAF1 fusion and pathogenic variants in CTNNB1 and CDKN2A. Anti-CTLA4/anti-PD1 combination immunotherapy failed to control tumor progression. In the absence of other actionable variants the patient was administered MEK inhibitor therapy on the basis of its potential action against RAF1 fusions. This resulted in a profound and clinically significant response. We demonstrated that GOLGA4-RAF1 expression was associated with ERK activation, elevated expression of the RAS/RAF downstream co-effector ETV5, and a high Ki67 index. These findings provide a rationale for the dramatic response to targeted therapy. This study shows that thorough molecular characterization of treatment-resistant cancers can identify therapeutic targets and personalize management, leading to improved patient outcomes.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23057
DOI: 10.1172/JCI123089
PubMed URL: 30835257
Type: Journal Article
Subjects: Cancer
Genetics
Melanoma
Molecular pathology
Oncology
Appears in Collections:Journal articles

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