Related Experiment Video
Updated: Sep 16, 2025
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Clinical Significance of TERT Promoter Mutations in Neuroblastoma
Natasha Persaud1, Gunes Gundem2, Brian H Kushner1
1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Purpose:
Telomere maintenance mechanisms including MYCN amplification (MYCN-A) (via upregulated telomerase reverse transcriptase [TERT] expression), TERT rearrangements (TERT-RA), and ATRX mutations confer neoplastic immortality in neuroblastoma (NB) cells. Clinical characterization of patients with NB harboring activating somatic TERT promoter point mutations (TERT-PM) in NB may improve stratification.
Methods:
To identify TERT-PM and TERT-RA, tumors were profiled by the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets targeted next-generation sequencing platform and whole-genome sequencing, respectively. Associated clinical outcomes were studied.
Results:
TERT-PM and TERT-RA were detected in 17 of 603 (2.8%) and 31of 168 (18.4%) tumors from individual patients, respectively. The median age at diagnosis was 32 (range, 15-79) and 48 (range, 3-168) months for TERT-PM and TERT-RA, respectively. TERT-PM were located at canonical hotspots (C228T [16/17] and C250T [1/17]) and were concurrent with MYCN-A in 9 of 17 (53%). By contrast, MYCN-A occurred in 1 of 31 TERT-RA tumors. Most patients with TERT-PM had stage M (94%) and high-risk NB (HR-NB) (81%) at diagnosis. Twenty-eight patients with TERT-RA had HR-NB (90%). After risk appropriate therapy, complete response was achieved in 7 of 17 (41%) and 17 of 31 (55%) patients with TERT-PM and TERT-RA, respectively. The median progression-free (PFS) and overall survival (OS) were 9.7 ± 1.2 and 16.5 ± 2 months for patients with TERT-PM. Corresponding PFS/OS for patients with TERT-RA were 20 ± 6.4/56.8 ± 8.6 months (P = .015 for OS). Excluding MYCN-A status produced no significant survival difference (P > .1) between the two groups. CNS relapse occurred in 11 of 31 (35%) patients with TERT-RA versus 1 of 17 (6%) patients with TERT-PM.
Conclusion:
TERT-PM is rarer than TERT-RA but both are associated with HR-NB and poor prognosis. MYCN-A frequently co-occurs with TERT-PM and might represent an ultra-high-risk subset of patients.
More Related Videos
09:33Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
08:57Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors
Published on: May 17, 2024
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...