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Journal of Cancer Research and Clinical Oncology

Erschienen in:

28.11.2017 | Original Article – Cancer Research

Analysis of TSC1 mutation spectrum in mucosal melanoma

verfasst von: Meng Ma, Jie Dai, Tianxiao Xu, Sifan Yu, Huan Yu, Huan Tang, Junya Yan, Xiaowen Wu, Jiayi Yu, Zhihong Chi, Lu Si, Chuanliang Cui, Xinan Sheng, Yan Kong, Jun Guo

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2018

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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 TSC1 and evaluated its correlation with the clinicopathological features of mucosal melanoma.

Methods

We collected 91 mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 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 TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007).

Conclusions

Our findings suggest that TSC1 mutations are frequent in mucosal melanoma. TSC1 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 TSC1 mutations for effective and specific drug therapy for mucosal melanoma.

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Titel: Analysis of TSC1 mutation spectrum in mucosal melanoma
verfasst von: Meng Ma
Jie Dai
Tianxiao Xu
Sifan Yu
Huan Yu
Huan Tang
Junya Yan
Xiaowen Wu
Jiayi Yu
Zhihong Chi
Lu Si
Chuanliang Cui
Xinan Sheng
Yan Kong
Jun Guo
Publikationsdatum: 28.11.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2550-z

Springer Medizin

Analysis of TSC1 mutation spectrum in mucosal melanoma