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Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients

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 burde...

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Autores principales: Hilke, Franz J., Sinnberg, Tobias, Gschwind, Axel, Niessner, Heike, Demidov, German, Amaral, Teresa, Ossowski, Stephan, Bonzheim, Irina, Röcken, Martin, Riess, Olaf, Garbe, Claus, Schroeder, Christopher, Forschner, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563780/
https://www.ncbi.nlm.nih.gov/pubmed/32825510
http://dx.doi.org/10.3390/cancers12092359
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author Hilke, Franz J.
Sinnberg, Tobias
Gschwind, Axel
Niessner, Heike
Demidov, German
Amaral, Teresa
Ossowski, Stephan
Bonzheim, Irina
Röcken, Martin
Riess, Olaf
Garbe, Claus
Schroeder, Christopher
Forschner, Andrea
author_facet Hilke, Franz J.
Sinnberg, Tobias
Gschwind, Axel
Niessner, Heike
Demidov, German
Amaral, Teresa
Ossowski, Stephan
Bonzheim, Irina
Röcken, Martin
Riess, Olaf
Garbe, Claus
Schroeder, Christopher
Forschner, Andrea
author_sort Hilke, Franz J.
collection PubMed
description 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 BRAF and NRAS, we frequently observed CDKN2A deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting PDGFRA, KIT, CDK4, RICTOR, CCND2 and CHEK2. Uveal melanoma often had somatic SNVs in GNA11/Q and amplification of MYC in all cases. A significantly higher incidence of BRAF V600 mutations and EGFR amplifications, PTEN and TP53 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.
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spelling pubmed-75637802020-10-27 Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients Hilke, Franz J. Sinnberg, Tobias Gschwind, Axel Niessner, Heike Demidov, German Amaral, Teresa Ossowski, Stephan Bonzheim, Irina Röcken, Martin Riess, Olaf Garbe, Claus Schroeder, Christopher Forschner, Andrea Cancers (Basel) Article 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 BRAF and NRAS, we frequently observed CDKN2A deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting PDGFRA, KIT, CDK4, RICTOR, CCND2 and CHEK2. Uveal melanoma often had somatic SNVs in GNA11/Q and amplification of MYC in all cases. A significantly higher incidence of BRAF V600 mutations and EGFR amplifications, PTEN and TP53 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. MDPI 2020-08-20 /pmc/articles/PMC7563780/ /pubmed/32825510 http://dx.doi.org/10.3390/cancers12092359 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hilke, Franz J.
Sinnberg, Tobias
Gschwind, Axel
Niessner, Heike
Demidov, German
Amaral, Teresa
Ossowski, Stephan
Bonzheim, Irina
Röcken, Martin
Riess, Olaf
Garbe, Claus
Schroeder, Christopher
Forschner, Andrea
Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title_full Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title_fullStr Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title_full_unstemmed Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title_short Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
title_sort distinct mutation patterns reveal melanoma subtypes and influence immunotherapy response in advanced melanoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563780/
https://www.ncbi.nlm.nih.gov/pubmed/32825510
http://dx.doi.org/10.3390/cancers12092359
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