Research Papers:

Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations

Ioana Cosgarea, Selma Ugurel, Antje Sucker, Elisabeth Livingstone, Lisa Zimmer, Mirjana Ziemer, Jochen Utikal, Peter Mohr, Christiane Pfeiffer, Claudia Pföhler, Uwe Hillen, Susanne Horn, Dirk Schadendorf, Klaus Griewank _ and Alexander Roesch

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Oncotarget. 2017; 8:40683-40692. https://doi.org/10.18632/oncotarget.16542

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Ioana Cosgarea1, Selma Ugurel1, Antje Sucker1, Elisabeth Livingstone1, Lisa Zimmer1, Mirjana Ziemer2, Jochen Utikal3, Peter Mohr4, Christiane Pfeiffer5, Claudia Pföhler6, Uwe Hillen1, Susanne Horn1, Dirk Schadendorf1, Klaus G. Griewank1,* and Alexander Roesch1,*

1Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany

2Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Germany

3Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany

4Department of Dermatology, Elbe Klinikum Buxtehude, Buxtehude, Germany

5Department of Dermatology, Klinikum Augsburg, Augsburg, Germany

6Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany

*These authors have contributed equally to this work

Correspondence to:

Klaus G. Griewank, email: [email protected]

Alexander Roesch, email: [email protected]

Keywords: mucosal melanoma, NF1, RAS, sequencing, melanoma

Received: December 28, 2016    Accepted: February 15, 2017    Published: March 24, 2017


Purpose: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown.

Experimental Design and Results: In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples.

Conclusions: Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors.

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