Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis
Abstract Background Most primary cutaneous melanomas have pathogenesis driven by ultraviolet exposure and genetic mutations, whereas acral lentiginous melanoma (ALM) and metastatic melanoma are much less, if at all, linked with the former. Thus, we evaluated both ultraviolet related and non‐ultravio...
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2024-09-01
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| Online Access: | https://doi.org/10.1002/cam4.70199 |
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| author | Nilesh Kodali Simona Alomary Abhijit Bhattaru Ahmed Eldaboush Robert A. Schwartz Shari R. Lipner |
| author_facet | Nilesh Kodali Simona Alomary Abhijit Bhattaru Ahmed Eldaboush Robert A. Schwartz Shari R. Lipner |
| author_sort | Nilesh Kodali |
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| description | Abstract Background Most primary cutaneous melanomas have pathogenesis driven by ultraviolet exposure and genetic mutations, whereas acral lentiginous melanoma (ALM) and metastatic melanoma are much less, if at all, linked with the former. Thus, we evaluated both ultraviolet related and non‐ultraviolet related melanomas. Mutations in the MUC16 and TTN genes commonly occur concurrently in these melanoma patients, but their combined prognostic significance stratified by gender and cancer subtype remains unclear. Methods The cBioPortal database was queried for melanoma studies and returned 16 independent studies. Data from 2447 melanoma patients were utilized including those with ALM, cutaneous melanoma (CM), and melanoma of unknown primary (MUP). Patients were grouped based on the presence or absence of MUC16 and TTN mutations. Univariate Cox regression and Student's t‐tests were used to analyze hazard ratios and total mutation count comparisons, respectively. Results TTN mutations, either alone or concurrently with MUC16 mutations, significantly correlated with worse prognosis overall, in both genders, and in CM patients. ALM patients with both mutations had better prognoses than CM patients, while ALM patients with neither mutation had worse prognosis than CM patients. For MUP patients, only MUC16 mutations correlated with worse prognosis. ALM patients with neither MUC16 nor TTN mutations had significantly more total mutations than MUP patients, followed by CM patients. Conclusion TTN mutations are a potential marker of poor prognosis in melanoma, which is amplified in the presence of concurrent MUC16 mutations. ALM patients with neither gene mutations had worse prognosis, suggesting a protective effect of having both MUC16 and TTN mutations. Only MUC16 mutations conferred a worse prognosis for MUP patients. Comprehensive genetic profiling in melanoma patients may facilitate personalized treatment strategies to optimize patient outcomes. |
| format | Article |
| id | doaj-art-1f4e67722d8c410b9e47fbaa13849fe9 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-1f4e67722d8c410b9e47fbaa13849fe92025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70199Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysisNilesh Kodali0Simona Alomary1Abhijit Bhattaru2Ahmed Eldaboush3Robert A. Schwartz4Shari R. Lipner5Rutgers New Jersey Medical School Newark New Jersey USARutgers New Jersey Medical School Newark New Jersey USARutgers New Jersey Medical School Newark New Jersey USADepartment of Dermatology Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USARutgers New Jersey Medical School Newark New Jersey USADepartment of Dermatology Weill Cornell Medicine New York New York USAAbstract Background Most primary cutaneous melanomas have pathogenesis driven by ultraviolet exposure and genetic mutations, whereas acral lentiginous melanoma (ALM) and metastatic melanoma are much less, if at all, linked with the former. Thus, we evaluated both ultraviolet related and non‐ultraviolet related melanomas. Mutations in the MUC16 and TTN genes commonly occur concurrently in these melanoma patients, but their combined prognostic significance stratified by gender and cancer subtype remains unclear. Methods The cBioPortal database was queried for melanoma studies and returned 16 independent studies. Data from 2447 melanoma patients were utilized including those with ALM, cutaneous melanoma (CM), and melanoma of unknown primary (MUP). Patients were grouped based on the presence or absence of MUC16 and TTN mutations. Univariate Cox regression and Student's t‐tests were used to analyze hazard ratios and total mutation count comparisons, respectively. Results TTN mutations, either alone or concurrently with MUC16 mutations, significantly correlated with worse prognosis overall, in both genders, and in CM patients. ALM patients with both mutations had better prognoses than CM patients, while ALM patients with neither mutation had worse prognosis than CM patients. For MUP patients, only MUC16 mutations correlated with worse prognosis. ALM patients with neither MUC16 nor TTN mutations had significantly more total mutations than MUP patients, followed by CM patients. Conclusion TTN mutations are a potential marker of poor prognosis in melanoma, which is amplified in the presence of concurrent MUC16 mutations. ALM patients with neither gene mutations had worse prognosis, suggesting a protective effect of having both MUC16 and TTN mutations. Only MUC16 mutations conferred a worse prognosis for MUP patients. Comprehensive genetic profiling in melanoma patients may facilitate personalized treatment strategies to optimize patient outcomes.https://doi.org/10.1002/cam4.70199demographicsmelanomaMUC16survival outcomesTTN |
| spellingShingle | Nilesh Kodali Simona Alomary Abhijit Bhattaru Ahmed Eldaboush Robert A. Schwartz Shari R. Lipner Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis Cancer Medicine demographics melanoma MUC16 survival outcomes TTN |
| title | Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis |
| title_full | Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis |
| title_fullStr | Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis |
| title_full_unstemmed | Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis |
| title_short | Gender and melanoma subtype‐based prognostic implications of MUC16 and TTN co‐occurrent mutations in melanoma: A retrospective multi‐study analysis |
| title_sort | gender and melanoma subtype based prognostic implications of muc16 and ttn co occurrent mutations in melanoma a retrospective multi study analysis |
| topic | demographics melanoma MUC16 survival outcomes TTN |
| url | https://doi.org/10.1002/cam4.70199 |
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