Journal Article

DKFZ-2023-00819

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clinical, histopathological and molecular features of dedifferentiated melanomas: An EORTC Melanoma Group Retrospective Analysis.

Hench, J. ; Mihic-Probst, D. ; Agaimy, A. ; Frank, S. ; Meyer, P. ; Hultschig, C. ; Simi, S. ; Alos, L. ; Balamurugan, T. ; Blokx, W. ; Bosisio, F. ; Cappellesso, R. ; Griewank, K.DKFZ* ; Hadaschik, E.DKFZ* ; van Kempen, L. C. ; Kempf, W. ; Lentini, M. ; Mazzucchelli, L. ; Rinaldi, G. ; Rutkowski, P. ; Schadendorf, D.DKFZ* ; Schilling, B. ; Szumera-Cieckiewicz, A. ; van den Oord, J. ; Mandalà, M. ; Massi, D. ; Group, E. M. (Collaboration Author)

2023
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ejca.2023.03.032

Abstract: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.

Keyword(s): Copy number profiling ; DNA methylation ; Dedifferentiated melanoma ; Epigenetics

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Contributing Institute(s):

1. DKTK ED ES zentral (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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