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Coexistence of TERT promoter and BRAF mutations in cutaneous melanoma is associated with more clinicopathological features of aggressiveness

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Abstract

The recently described telomerase reverse transcriptase (TERT) promoter mutations are recurrent in cutaneous melanoma. Several authors have described an association between these molecular alterations, some histological parameters, and patient survival. BRAF mutations are very frequent in melanoma, but their actual role in the evolution of the disease is still unclear. Here, we investigated the relationship of TERT promoter mutations and BRAF mutations with the most relevant clinicopathological parameters, individually and coexisting, in order to evaluate their role as independent prognostic markers and to determine the effect of their coexistence. A TERT promoter alteration was found in 20 of 53 cases (38 %), significantly associated with histological type, increasing tumor thickness and mitotic rate, more advanced pathologic tumor (pT) stage, and absence of regression. A BRAF mutation was found in 21 of 53 cases (40 %), significantly associated with tumor thickness and presence of metastases in the sentinel lymph node. Coexistence of a TERT promoter and BRAF mutation was detected in 11 of 53 cases (21 %). This was associated with increasing thickness, high mitotic rate, lymph node metastasis, presence of ulceration, and absence of regression. Coexistence of a mutation in the TERT promoter and in the BRAF gene correlated with more prognostically relevant factors than either mutation alone. Our data lead us to hypothesize that TERT promoter and BRAF mutations cooperate in cutaneous melanoma. Further studies in larger cohorts of patients are needed to investigate how this synergistic effect is involved in the evolution of the disease.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy

    Elisabetta Macerola, Riccardo Giannini, Mirella Giordano, Cristina Niccoli, Fulvio Basolo & Gabriella Fontanini

  2. Unit of Pathological Anatomy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

    Barbara Loggini, Giulia Garavello & Agnese Proietti

  3. Program of Pleuropulmonary Pathology, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

    Gabriella Fontanini

Authors
  1. Elisabetta Macerola
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  2. Barbara Loggini
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  3. Riccardo Giannini
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  4. Giulia Garavello
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  5. Mirella Giordano
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  6. Agnese Proietti
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  8. Fulvio Basolo
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  9. Gabriella Fontanini
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Correspondence to Gabriella Fontanini.

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Macerola, E., Loggini, B., Giannini, R. et al. Coexistence of TERT promoter and BRAF mutations in cutaneous melanoma is associated with more clinicopathological features of aggressiveness. Virchows Arch 467, 177–184 (2015). https://doi.org/10.1007/s00428-015-1784-x

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  • DOI: https://doi.org/10.1007/s00428-015-1784-x

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