Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Cancer Med. 2024 Sep;13(17):e70199. doi: 10.1002/cam4.70199.
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.
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.
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.
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.
大多数原发性皮肤黑色素瘤的发病机制与紫外线暴露和基因突变有关，而肢端雀斑样黑色素瘤（ALM）和转移性黑色素瘤与前者的相关性则小得多，如果有的话。因此，我们评估了与紫外线相关和非紫外线相关的黑色素瘤。在这些黑色素瘤患者中，MUC16 和 TTN 基因的突变通常同时发生，但它们在性别和癌症亚型分层下的联合预后意义尚不清楚。
我们在 cBioPortal 数据库中查询了黑色素瘤研究，并返回了 16 项独立研究。我们利用了 2447 名黑色素瘤患者的数据，包括 ALM、皮肤黑色素瘤（CM）和不明原发灶黑色素瘤（MUP）患者。患者根据是否存在 MUC16 和 TTN 突变进行分组。采用单因素 Cox 回归和学生 t 检验分别分析危险比和总突变数比较。
TTN 突变，无论是单独存在还是与 MUC16 突变同时存在，都与总体预后不良显著相关，在两性和 CM 患者中均如此。同时存在这两种突变的 ALM 患者比 CM 患者预后更好，而同时不存在这两种突变的 ALM 患者比 CM 患者预后更差。对于 MUP 患者，只有 MUC16 突变与预后不良相关。同时不存在 MUC16 和 TTN 突变的 ALM 患者总突变数明显多于 MUP 患者，其次是 CM 患者。
TTN 突变是黑色素瘤不良预后的一个潜在标志物，在同时存在 MUC16 突变时更为明显。同时不存在这两种基因突变的 ALM 患者预后更差，提示同时存在 MUC16 和 TTN 基因突变具有保护作用。只有 MUC16 突变对 MUP 患者的预后有不利影响。对黑色素瘤患者进行全面的基因谱分析可能有助于制定个性化的治疗策略，以优化患者的预后。
