Molecular characterization of fast-growing melanomas - 27/01/22
, Nicolas Macagno, MD, PhD b, Anderson Loundou, PhD c, Eric Pellegrino, MSc d, L'houcine Ouafik, PhD d, Timothy Budden, PhD e, Piyushkumar Mundra, PhD f, Gabriela Gremel, PhD f, Victoria Akhras, MD g, Lijing Lin, PhD h, Martin Cook, MD f, Rajiv Kumar, PhD i, Jean-Jacques Grob, MD a, Eduardo Nagore, MD, PhD j, Richard Marais, PhD f, Amaya Virós, MD, PhD e, ⁎ Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : fast-growth melanoma, FGFR2 mutations, melanoma, mutations of poor prognosis
Abbreviations used : DMFS, FGMM, MSS, ROG, RFS
Plan
| Funding sources: Dr Gaudy-Marqueste received funding from the Société Française de Dermatologie (SFD), Collège des Enseignants en Dermatologie de France (CEDEF) and Fondation de France. Dr Nagore received funding from the Fondo de Investigación en Salud (FIS) PI15/01860, Instituto Carlos III, Spain. Dr Kumar received funding from the TRANSCAN (01KT15511) provided through the German Ministry of Education and Research (BMBF) and Deutsches KrebsForschungsZentrum. Dr Marais received funding through the Cancer Research United Kingdom (A27412) and Wellcome Trust (100282/Z/12/Z). As a Wellcome Beit Fellow, Dr Viros was personally funded by a Wellcome Intermediate Fellowship (110078/Z/15/Z) with additional work funded by Cancer Research United Kingdom (A27412) Leo Pharma Foundation and Royal Society RGS∖R1∖201222. The European Organisation for Research and Treatment of Cancer provided funding to study primary melanoma tumor markers. |
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| This work was presented during the 16th Virtual European Association of Dermato Oncology Congress, October 12-14, 2020 (virtual meeting). |
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| IRB approval status: Not applicable. |
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| Reprints not available from the authors. |
Vol 86 - N° 2
P. 312-321 - février 2022 Retour au numéro
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