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Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review

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Abstract

Background

Primary mucosal melanomas (PMMs) are rare and clinically heterogeneous, including head and neck (HNMs), vulvovaginal (VVMs), conjunctival (CjMs), anorectal (ARMs) and penile (PMs) melanomas. While the prognosis of advanced cutaneous melanoma has noticeably improved using treatments with immune checkpoint inhibitors (ICIs) and molecules targeting BRAF and MEK, few advances have been made for PMMs because of their poorer response to ICIs and their different genetic profile. This prompted us to conduct a systematic review of molecular studies of PMMs to clarify their pathogenesis and potential therapeutic targets.

Methods

All articles that examined gene mutations in PMMs were identified from the databases and selected based on predefined inclusion criteria. Mutation rate was calculated for all PMMs and each location group by relating the number of mutations identified to the total number of samples analysed.

Results

Among 1,581 studies identified, 88 were selected. Overall, the frequency of KIT, BRAF and NRAS mutation was 13.5%, 12.9% and 12.1%, respectively. KIT mutation ranged from 6.4% for CjMs to 16.6% for ARMs, BRAF mutation from 8.6% for ARMs to 31.1% for CjMs, and NRAS mutation from 6.2% for ARMs to 18.5% for CjMs. Among 101 other genes analysed, 33 had mutation rates over 10%, including TTN, TSC1, POM121, NF1, MTOR and SF3B1.

Conclusion

In addition to BRAF, NRAS and KIT genes commonly studied, our systematic review identified significantly mutated genes that have already been associated (e.g., TSC1, mTOR, POLE or ATRX) or could be associated with (future) targeted therapies.

PROSPERO ID: CRD42020185552

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Authors and Affiliations

  1. CHU Reims, Service de Pathologie, Reims, France

    Olivia Beaudoux & Aude Marchal

  2. Université de Reims Champagne-Ardenne, EA 7509: Immune Dysregulation and Tissue Remodelling in Cancer, Autoimmune and Inflammatory Diseases, Reims, France

    Olivia Beaudoux & Florent Grange

  3. Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France

    Jean-Baptiste Oudart

  4. CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire – MEDyC, Reims, France

    Jean-Baptiste Oudart

  5. CHU Reims, Pôle de Biologie, Service de Biochimie – Pharmacologie – Toxicologie, Reims, France

    Jean-Baptiste Oudart

  6. CHU Reims, Service d’Oncodermatologie, Reims, France

    Laurence Riffaud, Laetitia Visseaux & Florent Grange

  7. CHU Reims, Pôle de Biologie, Service de Génétique, Reims, France

    Anne-Sophie Lebre

  8. Université de Reims Champagne-Ardenne, Reims, France

    Anne-Sophie Lebre & Florent Grange

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  1. Olivia Beaudoux
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Data that support the findings of this study are available on request from the corresponding author.

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O. Beaudoux and F. Grange conceived of the presented idea and contributed to the design and implementation of the research. O. Beaudoux developed the theory and performed the analysis of the results. F. Grange and A.S. Lebre verified the analytical methods and supervised the findings of this work. All authors discussed the results, participated in the writing of the manuscript, and contributed to the final manuscript.

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Beaudoux, O., Oudart, JB., Riffaud, L. et al. Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review. Mol Diagn Ther 26, 189–202 (2022). https://doi.org/10.1007/s40291-021-00572-0

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