A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma G
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ORIGINAL RESEARCH ARTICLE
A Melanoma‑Tailored Next‑Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping Baptiste Louveau1,2,3 · Fanélie Jouenne1,2,3 · Pauline Têtu4 · Aurélie Sadoux1 · Aurélia Gruber1 · Eddie Lopes1 · Julie Delyon2,3,4 · Kevin Serror5 · Oren Marco5 · Laetitia Da Meda4 · Aminata Ndiaye6 · Alban Lermine6 · Nicolas Dumaz3 · Maxime Battistella2,3,7 · Barouyr Baroudjian4 · Céleste Lebbe2,3,4 · Samia Mourah1,2,3
© Springer Nature Switzerland AG 2020
Abstract Background Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies. Objective The objective of this study was to present such a customized next-generation sequencing panel in melanoma. Methods Melanoma patients with somatic molecular profiling performed as part of routine care were included. Highthroughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations. Results Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splicesite mutations. At least one alteration was detected in 368 (87.4%) lesions, with BRAF, NRAS, CDKN2A, CCND1, and MET as the most frequently altered genes. Among patients with BRAFV600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with RAS hotspot mutated lesions and in patients with neither BRAFV600 nor RAS hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively. Conclusions Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients’ clinical management.
1 Introduction Melanoma is an aggressive skin cancer with a poor prognosis when diagnosed at an advanced stage [1]. Recently, molecular deciphering has revealed a high number of Co-first authors: Baptiste Louveau and Fanélie Jouenne. Co-senior authors: Céleste Lebbe and Samia Mourah. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11523-020-00764-4) contains supplementary material, which is available to authorized users. * Sa
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