# Alternate Telomere Maintenance Mechanisms in High Risk Neuroblastoma as Prognostic Indicators and Therapeutic Targets Yr 1 to 5

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2021 · $59,991

## Abstract

We request a supplement for this grant to enable optimal completion of the original aims, and in
particular to enable using specific Aim 1 to re-define risk stratification for neuroblastoma within
the Children’s Oncology Group (COG).
The supplement will be used for work on Specific Aim 1 of the grant, which is:
Specific Aim 1. In high-risk NB determine the relationship of telomere maintenance
mechanisms (TMM), i.e. telomerase expression vs. alternate telomere maintenance (ALT)
phenotype, to clinical outcome, MYCN genomic amplification, 11q deletions, and ATRX
mutations. Low TERT expression is associated with favorable outcome in low/intermediate risk
NB (stages 1, 2, 4S). By contrast, low/negative TERT expression in high-risk NB has been
observed in patients with treatment-refractory tumors. In collaboration with the Children’s
Oncology Group (COG) we will categorize high-risk stage 4 NBs by TMM and determine the
relationship of TMM to clinical outcome and tumor molecular features.
A. In high-risk stage 4 NBs for which ATRX genotype is known assess TERT and TERC
expression, C-circle content, and telomere content to define subsets of tumors based on TMM:
1) telomerase-high, 2) ALT = telomerase negative/c-circle +, 3) EST = telomerase-low/C-circle
negative. Determine the association of TMM phenotype with ATRX mutations, telomere content,
and clinical outcome.
B. Confirm TERT and C-circle expression as NB prognostic markers in a validation set of
primary tumors.
C. Compare genome-wide RNA expression of telomerase-positive and ALT

## Key facts

- **NIH application ID:** 10366253
- **Project number:** 3R01CA217251-03S1
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** CHARLES Patrick REYNOLDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,991
- **Award type:** 3
- **Project period:** 2018-08-29 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366253

## Citation

> US National Institutes of Health, RePORTER application 10366253, Alternate Telomere Maintenance Mechanisms in High Risk Neuroblastoma as Prognostic Indicators and Therapeutic Targets Yr 1 to 5 (3R01CA217251-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10366253. Licensed CC0.

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