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- Title
Analysis of TSC1 mutation spectrum in mucosal melanoma.
- Authors
Ma, Meng; Dai, Jie; Xu, Tianxiao; Yu, Sifan; Yu, Huan; Tang, Huan; Yan, Junya; Wu, Xiaowen; Yu, Jiayi; Chi, Zhihong; Si, Lu; Cui, Chuanliang; Sheng, Xinan; Kong, Yan; Guo, Jun
- Abstract
Purpose: Mucosal melanoma is a relatively rare subtype of melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator <italic>TSC1</italic> and evaluated its correlation with the clinicopathological features of mucosal melanoma.Methods: We collected 91 mucosal melanoma samples for detecting <italic>TSC1</italic> mutations. All the coding exons of <italic>TSC1</italic> were amplified by PCR and subjected to Sanger sequencing. Expression level of <italic>TSC1</italic> encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1.Results: The overall mutation frequency of <italic>TSC1</italic> was found to be 17.6% (16/91 patients). <italic>TSC1</italic> mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with <italic>TSC1</italic> mutations, 14 different mutations were detected, affecting 11 different exons. <italic>TSC1</italic> mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with <italic>TSC1</italic> mutations had a worse outcome than patients without <italic>TSC1</italic> mutations (24.0 versus 34.0 months, <italic>P</italic> = 0.007).Conclusions: Our findings suggest that <italic>TSC1</italic> mutations are frequent in mucosal melanoma. <italic>TSC1</italic> mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of mucosal melanoma. Our data implicate the potential significance of <italic>TSC1</italic> mutations for effective and specific drug therapy for mucosal melanoma.
- Subjects
MELANOMA treatment; MTOR protein; GENETIC mutation; HAMARTIN; IMMUNOHISTOCHEMISTRY
- Publication
Journal of Cancer Research & Clinical Oncology, 2018, Vol 144, Issue 2, p257
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-017-2550-z