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Published on: June 7, 2019
Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review
Olivia Beaudoux1,2, Jean-Baptiste Oudart3,4,5, Laurence Riffaud6
1CHU Reims, Service de Pathologie, Reims, France. obeaudoux@chu-reims.fr.
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.
Insights
This review of primary mucosal melanomas (PMMs) found common mutations in KIT, BRAF, and NRAS genes. It also identified other significantly mutated genes, offering potential targets for future therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Primary mucosal melanomas (PMMs) are rare and diverse cancers with limited treatment advances compared to cutaneous melanoma.
- PMMs exhibit poorer responses to immune checkpoint inhibitors (ICIs) and distinct genetic profiles, necessitating further research into their pathogenesis.
- This study systematically reviewed molecular data to identify potential therapeutic targets for PMMs.
Approach:
- A systematic review was conducted, identifying and selecting studies that examined gene mutations in PMMs.
- Mutation rates were calculated for common genes (KIT, BRAF, NRAS) and other frequently mutated genes across different PMM subtypes.
- Data from 88 selected studies, analyzing 1,581 initially identified articles, were synthesized.
Key Points:
- The overall mutation frequencies were 13.5% for KIT, 12.9% for BRAF, and 12.1% for NRAS.
- Specific mutation rates varied by PMM subtype, with KIT mutations highest in anorectal melanomas (ARMs) and BRAF/NRAS mutations highest in conjunctival melanomas (CjMs).
- Beyond commonly studied genes, 33 other genes, including TTN, TSC1, MTOR, and SF3B1, showed mutation rates exceeding 10%.
Conclusions:
- The review identified significantly mutated genes in PMMs beyond the commonly analyzed KIT, BRAF, and NRAS.
- Genes such as TSC1, mTOR, POLE, and ATRX were highlighted as potentially targetable for future PMM therapies.
- Understanding these molecular alterations is crucial for developing targeted treatment strategies for PMMs.
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