Fiche publication
Date publication
août 2020
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr AMARAL Teresa Maria
Tous les auteurs :
Hilke FJ, Sinnberg T, Gschwind A, Niessner H, Demidov G, Amaral T, Ossowski S, Bonzheim I, Röcken M, Riess O, Garbe C, Schroeder C, Forschner A
Lien Pubmed
Résumé
The detection of somatic driver mutations by next-generation sequencing (NGS) is becoming increasingly important in the care of advanced melanoma patients. In our study, we evaluated the NGS results of 82 melanoma patients from clinical routine in 2017. Besides determining the tumor mutational burden (TMB) and annotation of all genetic driver alterations, we investigated their potential as a predictor for resistance to immune checkpoint inhibitors (ICI) and as a distinguishing feature between melanoma subtypes. Melanomas of unknown primary had a similar mutation pattern and TMB to cutaneous melanoma, which hints at its cutaneous origin. Besides the typical hotspot mutation in and , we frequently observed deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting , , , , and . Uveal melanoma often had somatic SNVs in and amplification of in all cases. A significantly higher incidence of V600 mutations and amplifications, and deletions was found in patients with disease progression while on ICI. Thus, NGS might help to characterize melanoma subtypes more precisely and to identify possible resistance mechanisms to ICI therapy. Nevertheless, NGS based studies, including larger cohorts, are needed to support potential genetic ICI resistance mechanisms.
Mots clés
Genome of advanced melanoma, TMB, acral, immune checkpoint inhibitors, melanoma of unknown origin, mucosal, next-generation sequencing, tumor mutation burden, uveal
Référence
Cancers (Basel). 2020 08 20;12(9):
