Molecular characterization of fast-growing melanomas.

Humans Melanoma / pathology Mutation Prognosis Prospective Studies Skin Neoplasms / pathology
FGFR2 mutations fast-growth melanoma melanoma mutations of poor prognosis

Journal

Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132

Informations de publication

Date de publication:
02 2022
Historique:
received: 25 01 2021
revised: 30 06 2021
accepted: 01 07 2021
pubmed: 20 7 2021
medline: 15 4 2022
entrez: 19 7 2021
Statut: ppublish

Résumé

The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied. To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth. Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma samples. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month). Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth. Single-center study, cohort size, potential memory bias, number of investigated genes. Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies.

Sections du résumé

BACKGROUND
The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied.
OBJECTIVE
To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth.
METHODS
Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma samples. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month).
RESULTS
Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth.
LIMITATIONS
Single-center study, cohort size, potential memory bias, number of investigated genes.
CONCLUSION
Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies.

Identifiants

DOI: 10.1016/j.jaad.2021.07.011 PMID: 34280484
pubmed: 34280484
pii: S0190-9622(21)02101-0
doi: 10.1016/j.jaad.2021.07.011
pii:
doi:

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

312-321

Subventions

Organisme : Wellcome Trust
ID : 110078/Z/15/Z
Pays : United Kingdom

Informations de copyright

Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest None disclosed.

Auteurs

Caroline Gaudy-Marqueste (C)

Aix Marseille University, Assistance Publique des Hopitaux de Marseille, Centre de Recherche en Cancérologie de Marseille Insitut National de la Santé Et de la Recherche Médicale U1068, Centre National de la Recherche Scientifique U7258, Centre Hospitalo-Universitaire Timone, Dermatology and Skin Cancer Department, Marseille, France. Electronic address: caroline.gaudy@ap-hm.fr.

Nicolas Macagno (N)

Aix Marseille University, Assistance Publique des Hopitaux de Marseille, Insitut National de la Santé Et de la Recherche Médicale, Marseille Medical Genetics, Centre Hospitalo-Universitaire Timone, Department of Pathology, Marseille, France.

Anderson Loundou (A)

Aix Marseille University, Santé Publique et Maladie Chroniques EA3279, Clinical Research Unit, Department of Public Health, Marseille, France.

Eric Pellegrino (E)

Aix Marseille Univ, Assistance Publique des Hopitaux de Marseille, Centre National de la Recherche Scientifique, Institute of NeuroPhysiopathology, Faculté de Médecine Secteur Nord, Service de Transfert d'Oncologie Biologique, Marseille, France.

L'houcine Ouafik (L)

Aix Marseille Univ, Assistance Publique des Hopitaux de Marseille, Centre National de la Recherche Scientifique, Institute of NeuroPhysiopathology, Faculté de Médecine Secteur Nord, Service de Transfert d'Oncologie Biologique, Marseille, France.

Timothy Budden (T)

Skin Cancer and Ageing Lab, Cancer Research United Kingdom Manchester Institute, The University of Manchester, Manchester, United Kingdom.

Piyushkumar Mundra (P)

Molecular Oncology, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.

Gabriela Gremel (G)

Molecular Oncology, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.

Victoria Akhras (V)

Department of Dermatology, St. George's National Health Service Foundation Trust, London, United Kingdom.

Lijing Lin (L)

Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.

Martin Cook (M)

Molecular Oncology, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.

Rajiv Kumar (R)

Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg, Germany.

Jean-Jacques Grob (JJ)

Aix Marseille University, Assistance Publique des Hopitaux de Marseille, Centre de Recherche en Cancérologie de Marseille Insitut National de la Santé Et de la Recherche Médicale U1068, Centre National de la Recherche Scientifique U7258, Centre Hospitalo-Universitaire Timone, Dermatology and Skin Cancer Department, Marseille, France.

Eduardo Nagore (E)

Department of Dermatology, Instituto Valenciano Oncología, València, Spain.

Richard Marais (R)

Molecular Oncology, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.

Amaya Virós (A)

Skin Cancer and Ageing Lab, Cancer Research United Kingdom Manchester Institute, The University of Manchester, Manchester, United Kingdom. Electronic address: Amaya.viros@cruk.manchester.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Molecular characterization of fast-growing melanomas.
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Molecular characterization of fast-growing melanomas.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Molecular characterization of fast-growing melanomas.
questionsmedicales.fr › Diagnostic › Pronostic › Molecular characterization of fast-growing melanomas.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Molecular characterization of fast-growing melanomas.
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Tumeurs cutanées › Molecular characterization of fast-growing melanomas.