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TERT promoter mutations in melanoma survival.

Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther and Sanjuan-Gimenez, Josefa, et al. (2016) In International Journal of Cancer 139(1). p.75-84
Abstract
Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at risk primary melanoma patients. In this study we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. DNA from 300 patients with stage I/II melanoma was sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression free and melanoma specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease free... (More)
Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at risk primary melanoma patients. In this study we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. DNA from 300 patients with stage I/II melanoma was sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression free and melanoma specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease free and melanoma specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease free survival was 2.25 (95%CI 1.2-4.4) and for melanoma specific survival 5.8 (95%CI 1.8-18.1). The effect of the mutations on melanoma-specific survival in non-carriers of variant allele of the polymorphism was significant (HR 4.4, 95%CI 1.3-14.9) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.4, 95%CI 0.1-0.9). The data in this study provides preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. This article is protected by copyright. All rights reserved. (Less)
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International Journal of Cancer
volume
139
issue
1
pages
75 - 84
publisher
John Wiley & Sons
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  • pmid:26875008
  • scopus:84959480782
  • wos:000374381400011
ISSN
0020-7136
DOI
10.1002/ijc.30042
language
English
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yes
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f99a4d78-ce55-49b2-a0c2-5c04bd968da5 (old id 8825527)
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http://www.ncbi.nlm.nih.gov/pubmed/26875008?dopt=Abstract
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2016-03-01 14:15:53
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2017-10-22 03:18:48
@article{f99a4d78-ce55-49b2-a0c2-5c04bd968da5,
  abstract     = {Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at risk primary melanoma patients. In this study we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. DNA from 300 patients with stage I/II melanoma was sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression free and melanoma specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease free and melanoma specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease free survival was 2.25 (95%CI 1.2-4.4) and for melanoma specific survival 5.8 (95%CI 1.8-18.1). The effect of the mutations on melanoma-specific survival in non-carriers of variant allele of the polymorphism was significant (HR 4.4, 95%CI 1.3-14.9) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.4, 95%CI 0.1-0.9). The data in this study provides preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. This article is protected by copyright. All rights reserved.},
  author       = {Nagore, Eduardo and Heidenreich, Barbara and Rachakonda, Sívaramakrishna and Garcia-Casado, Zaida and Requena, Celia and Soriano, Virtudes and Frank, Christoph and Traves, Victor and Quecedo, Esther and Sanjuan-Gimenez, Josefa and Hemminki, Kari and Teresa Landi, Maria and Kumar, Rajiv},
  issn         = {0020-7136},
  language     = {eng},
  month        = {02},
  number       = {1},
  pages        = {75--84},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {TERT promoter mutations in melanoma survival.},
  url          = {http://dx.doi.org/10.1002/ijc.30042},
  volume       = {139},
  year         = {2016},
}