Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations, and DNA methylation profiling

Klaus G. Griewank, Christian Koelsche, Johannes A.P. van de Nes, Daniel Schrimpf, Marco Gessi, Inga Moller, Antje Sucker, Richard A. Scolyer, Michael E. Buckland, Rajmohan Murali, Torsten Pietsch, Andreas von Deimling, Dirk Schadendorf

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria may be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Experimental Design: Targeted next-generation sequencing, array-based genome-wide methylation analysis, and BAP1 IHC were performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, including 47 primary tumors of the central nervous system, 16 uveal melanomas, 13 cutaneous melanoma metastases, and 2 blue nevus–like melanomas. Gene mutation, DNA-methylation, and copy-number profiles were correlated with clinicopathologic features. Results: Combining mutation, copy-number, and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas, and blue nevus–like melanoma showed common DNA-methylation, copy-number alteration, and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Conclusions: Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma, and blue nevus–like melanoma share molecular similarity with chromosome 3 and BAP1 alterations, markers of poor prognosis.

Original languageEnglish
Pages (from-to)4494-4504
Number of pages11
JournalClinical Cancer Research
Volume24
Issue number18
DOIs
Publication statusPublished - Sep 15 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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