快速生长型黑色素瘤的分子特征

Molecular characterization of fast-growing melanomas.

作者信息

Gaudy-Marqueste Caroline, Macagno Nicolas, Loundou Anderson, Pellegrino Eric, Ouafik L'houcine, Budden Timothy, Mundra Piyushkumar, Gremel Gabriela, Akhras Victoria, Lin Lijing, Cook Martin, Kumar Rajiv, Grob Jean-Jacques, Nagore Eduardo, Marais Richard, Virós Amaya

机构信息

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.

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.

出版信息

J Am Acad Dermatol. 2022 Feb;86(2):312-321. doi: 10.1016/j.jaad.2021.07.011. Epub 2021 Jul 16.

DOI:10.1016/j.jaad.2021.07.011

PMID:34280484

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.

摘要

背景

原发性黑色素瘤的生长速度是侵袭性的有力预测指标，但快速生长型黑色素瘤（FGMM）的突变谱以及对高死亡风险患者进行分层的可能性尚未得到全面研究。

目的

研究厚度≥1mm的原发性皮肤黑色素瘤按生长速度分层后的流行病学、临床和突变谱。

方法

观察性前瞻性研究。对福尔马林固定、石蜡包埋的原发性黑色素瘤样本中的40个黑色素瘤驱动基因进行深度靶向测序。比较FGMM（生长速度>0.5mm/月）和非FGMM（生长速度≤0.5mm/月）。

结果

共纳入200例患者，其中70例为FGMM。FGMM组的无复发生存率较低（P = 0.014）。FGMM在40个基因中预测的有害突变数量高于非FGMM（P = 0.033）。溃疡（P = 0.032）、厚度（P = 0.006）、较低的阳光暴露（P = 0.049）和成纤维细胞生长因子受体2（FGFR2）突变（P = 0.037）与快速生长显著相关。