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Article

Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas

1
Department of Pathology, Poznan University Medical Sciences and Greater Poland Cancer Center, 61-701 Poznan, Poland
2
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
3
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
4
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
5
Department of Pathology, Kyoto University Hospital, Kyoto 606-8507, Japan
6
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
7
Department of Pathology, Medical University of Gdansk, 80-210 Gdansk, Poland
8
Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 31-115 Cracow Branch, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Barbara Stecca and Laura Poliseno
Cells 2021, 10(9), 2216; https://doi.org/10.3390/cells10092216
Received: 3 August 2021 / Revised: 22 August 2021 / Accepted: 25 August 2021 / Published: 27 August 2021
(This article belongs to the Special Issue Advances in Cellular and Molecular Research in Melanoma)
Background: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. Methods: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989–2020 in several clinical institutions were analyzed. NRAS, KIT, BRAF, IGF2R and SF3B1 mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (BRAF, NRAS, NF1)-negative cases, APC, KIT and KRAS are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. NRAS, KIT, BRAF, IGF2R and SF3B1 mutations are detected in 19% (37/198), 22% (44/197), 12% (25/201), 16% (22/138) and 15% (20/133) of cases, respectively. In univariate analyses, advanced stage (p = 0.016), 65 years or older (p = 0.048) and presence of ulceration (p = 0.027) are significantly correlated with worse overall survival (OS), respectively. NRAS mutation significantly correlates with worse OS (p = 0.028) and worse melanoma-specific survival (MSS) (p = 0.03) for all cases of mucosal melanomas. In multivariate analyses, NRAS mutation remains as an independent predictor of worse OS (p = 0.036) and worse MSS (p = 0.024). Conclusion: NRAS mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated IGF2R in mucosal melanomas remains unclear. View Full-Text
Keywords: mucosal melanoma; vulvovaginal; sinonasal; anorectal; NRAS; KIT; BRAF; SF3B1; IGF2R mucosal melanoma; vulvovaginal; sinonasal; anorectal; NRAS; KIT; BRAF; SF3B1; IGF2R
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MDPI and ACS Style

Wróblewska, J.P.; Dias-Santagata, D.; Ustaszewski, A.; Wu, C.-L.; Fujimoto, M.; Selim, M.A.; Biernat, W.; Ryś, J.; Marszalek, A.; Hoang, M.P. Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas. Cells 2021, 10, 2216. https://doi.org/10.3390/cells10092216

AMA Style

Wróblewska JP, Dias-Santagata D, Ustaszewski A, Wu C-L, Fujimoto M, Selim MA, Biernat W, Ryś J, Marszalek A, Hoang MP. Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas. Cells. 2021; 10(9):2216. https://doi.org/10.3390/cells10092216

Chicago/Turabian Style

Wróblewska, Joanna P., Dora Dias-Santagata, Adam Ustaszewski, Cheng-Lin Wu, Masakazu Fujimoto, M. Angelica Selim, Wojciech Biernat, Janusz Ryś, Andrzej Marszalek, and Mai P. Hoang. 2021. "Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas" Cells 10, no. 9: 2216. https://doi.org/10.3390/cells10092216

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