Distinct genomic features in a retrospective cohort of mucosal, acral, and vulvovaginal melanomas - 14/04/23
, Pedram Gerami, MD a, f, ⁎ Abstract |
Background |
Compared with sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors, but their genetic heterogeneity is not well studied.
Objective |
We investigated the genomic profile of acral, mucosal, and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features.
Methods |
We performed whole transcriptome messenger RNA and DNA (1711 genes) sequencing, messenger RNA expression profiling, tumor mutational burden, ultraviolet signature, and copy number variants analysis on 29 volar/digital acral, 7 mucosal, and 6 vulvovaginal melanomas.
Results |
There was significant genetic heterogeneity, particularly in acral melanomas, with 36% having BRAF alterations, whereas other melanomas had none (P = .0159). Nonzero ultraviolet signatures were more frequent in acral melanomas, suggesting greater ultraviolet involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified, such as AURKA and ERBB2, in mucosal and acral melanomas, respectively.
Limitations |
The sample size was a small.
Conclusion |
There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas.
Le texte complet de cet article est disponible en PDF.Key words : acral, AURKA, BRAF, CDKN2A, cell cycle and proliferation, CNV, DNA, ERBB2, expression, genomic, head and neck, HER2/Neu, KIT, melanoma, mRNA, mucosal, NF1, NRAS, sequencing, sun-exposed, sun-protected, TERT, TMB, ultraviolet, vaginal, vulvar, vulvovaginal
Abbreviations used : CNV, mRNA, PCA, TMB, UV, UVR
Plan
| Katherine Shi and Bin Zhang contributed equally to this article. Dr Zou and Dr Gerami contributed equally to this article. |
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| Funding sources: This study was partially supported by the IDP Foundation and the Melanoma Research Foundation (SP0043559). |
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| Conflicts of interest: Drs Igartua, Beaubier, Taxter, and White are employees at Tempus, Inc. Dr Gerami has served as a consultant for Myriad Genomics, DermTech Int, Merck, and Castle Biosciences and has received honoraria for this. Authors Shi, B. Zhang, Kong, Y. Zhang, Mohan, Quan, Panah, Isales, and Zou have no conflicts of interest to declare. |
Vol 88 - N° 5
P. 1051-1059 - mai 2023 Retour au numéro
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