TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms

• Type of Material: Article
• Authors: Seungjae Lee, St Jude Children's Research Hospital; Raymond L. Barnhill, Institut Curie; Reinhard Dummer, University Hospital Zurich; James Dalton, St Jude Children's Research Hospital; Jianrong Wu, St Jude Children's Research Hospital; Alberto Pappo, St Jude Children's Research Hospital; Armita Bahrami, Emory University
• Language: English
• Date: 2015-06-10
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Macmillan Publishers Limited
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep11200
• Title of Journal or Parent Work: SCIENTIFIC REPORTS
• Volume: 5
• Issue: 1
• Start Page: 11200
• End Page: 11200
• Grant/Funding Information: Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under Award Number P30CA021765 and by the American Lebanese Syrian Associated Charities (ALSAC).
• Keywords: TUMORS; DIAGNOSIS; MELANOMA; CATALYTIC SUBUNIT; FISH; CHILDREN; IN-SITU HYBRIDIZATION; Multidisciplinary Sciences; Science & Technology; LYMPH-NODE BIOPSY; Science & Technology - Other Topics; ADOLESCENTS; TELOMERASE
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Spitzoid neoplasms constitute a morphologically distinct category of melanocytic tumors, encompassing Spitz nevus (benign), atypical Spitz tumor (intermediate malignant potential), and spitzoid melanoma (fully malignant). Currently, no reliable histopathological criteria or molecular marker is known to distinguish borderline from overtly malignant neoplasms. Because TERT promoter (TERT-p) mutations are common in inherently aggressive cutaneous conventional melanoma, we sought to evaluate their prognostic significance in spitzoid neoplasms. We analyzed tumors labeled as atypical Spitz tumor or spitzoid melanoma from 56 patients with available follow-up data for the association of TERT-p mutations, biallelic CDKN2A deletion, biallelic PTEN deletion, kinase fusions, BRAF/NRAS mutations, nodal status, and histopathological parameters with risk of hematogenous metastasis. Four patients died of disseminated disease and 52 patients were alive and disease free without extranodal metastasis (median follow-up, 32.5 months). We found TERT-p mutations in samples from the 4 patients who developed hematogenous metastasis but in none of tumors from patients who had favorable outcomes. Presence of TERT-p mutations was the most significant predictor of haematogenous dissemination (P < 0.0001) among variables analyzed. We conclude that TERT-p mutations identify a clinically high-risk subset of patients with spitzoid tumors. Application of TERT-p mutational assays for risk stratification in the clinic requires large-scale validation.