Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas
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. <i>NRAS</i>, <i>KIT</i>, <i...
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MDPI AG
2021-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2216 |
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| author | Joanna P. Wróblewska Dora Dias-Santagata Adam Ustaszewski Cheng-Lin Wu Masakazu Fujimoto M. Angelica Selim Wojciech Biernat Janusz Ryś Andrzej Marszalek Mai P. Hoang |
| author_facet | Joanna P. Wróblewska Dora Dias-Santagata Adam Ustaszewski Cheng-Lin Wu Masakazu Fujimoto M. Angelica Selim Wojciech Biernat Janusz Ryś Andrzej Marszalek Mai P. Hoang |
| author_sort | Joanna P. Wróblewska |
| collection | DOAJ |
| description | 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. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (<i>BRAF</i>, <i>NRAS</i>, <i>NF1</i>)-negative cases, <i>APC</i>, <i>KIT</i> and <i>KRAS</i> are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> 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 (<i>p</i> = 0.016), 65 years or older (<i>p</i> = 0.048) and presence of ulceration (<i>p</i> = 0.027) are significantly correlated with worse overall survival (OS), respectively. <i>NRAS</i> mutation significantly correlates with worse OS (<i>p</i> = 0.028) and worse melanoma-specific survival (MSS) (<i>p</i> = 0.03) for all cases of mucosal melanomas. In multivariate analyses, <i>NRAS</i> mutation remains as an independent predictor of worse OS (<i>p</i> = 0.036) and worse MSS (<i>p</i> = 0.024). Conclusion: <i>NRAS</i> mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated <i>IGF2R</i> in mucosal melanomas remains unclear. |
| first_indexed | 2024-03-10T07:49:51Z |
| format | Article |
| id | doaj.art-ecfb73e88a5a4fe68e81a3afa87628e2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:49:51Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ecfb73e88a5a4fe68e81a3afa87628e22023-11-22T12:22:37ZengMDPI AGCells2073-44092021-08-01109221610.3390/cells10092216Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal MelanomasJoanna P. Wróblewska0Dora Dias-Santagata1Adam Ustaszewski2Cheng-Lin Wu3Masakazu Fujimoto4M. Angelica Selim5Wojciech Biernat6Janusz Ryś7Andrzej Marszalek8Mai P. Hoang9Department of Pathology, Poznan University Medical Sciences and Greater Poland Cancer Center, 61-701 Poznan, PolandDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAInstitute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, PolandDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanDepartment of Pathology, Kyoto University Hospital, Kyoto 606-8507, JapanDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USADepartment of Pathology, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 31-115 Cracow Branch, PolandDepartment of Pathology, Poznan University Medical Sciences and Greater Poland Cancer Center, 61-701 Poznan, PolandDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USABackground: 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. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (<i>BRAF</i>, <i>NRAS</i>, <i>NF1</i>)-negative cases, <i>APC</i>, <i>KIT</i> and <i>KRAS</i> are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> 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 (<i>p</i> = 0.016), 65 years or older (<i>p</i> = 0.048) and presence of ulceration (<i>p</i> = 0.027) are significantly correlated with worse overall survival (OS), respectively. <i>NRAS</i> mutation significantly correlates with worse OS (<i>p</i> = 0.028) and worse melanoma-specific survival (MSS) (<i>p</i> = 0.03) for all cases of mucosal melanomas. In multivariate analyses, <i>NRAS</i> mutation remains as an independent predictor of worse OS (<i>p</i> = 0.036) and worse MSS (<i>p</i> = 0.024). Conclusion: <i>NRAS</i> mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated <i>IGF2R</i> in mucosal melanomas remains unclear.https://www.mdpi.com/2073-4409/10/9/2216mucosal melanomavulvovaginalsinonasalanorectal<i>NRAS</i><i>KIT</i> |
| spellingShingle | Joanna P. Wróblewska Dora Dias-Santagata Adam Ustaszewski Cheng-Lin Wu Masakazu Fujimoto M. Angelica Selim Wojciech Biernat Janusz Ryś Andrzej Marszalek Mai P. Hoang Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas Cells mucosal melanoma vulvovaginal sinonasal anorectal <i>NRAS</i> <i>KIT</i> |
| title | Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas |
| title_full | Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas |
| title_fullStr | Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas |
| title_full_unstemmed | Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas |
| title_short | Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas |
| title_sort | prognostic roles of i braf i i kit i i nras i i igf2r i and i sf3b1 i mutations in mucosal melanomas |
| topic | mucosal melanoma vulvovaginal sinonasal anorectal <i>NRAS</i> <i>KIT</i> |
| url | https://www.mdpi.com/2073-4409/10/9/2216 |
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