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Journal Club

Tumor/Skull Base

TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Proc Natl Acad Sci U S A | 2013

Rapid review note

Journal Club is a rapid, AI-assisted appraisal layer. It highlights study design, effect estimates, and practice relevance, but it is still a briefing, not a replacement for the paper.

For education only. Not medical advice.

Paper snapshot

Rapid study overview

Open paper

DOI

10.1073/pnas.1303607110

PMID

23530248

PICO

Population

1,230 tumors of 60 different types, including gliomas

Intervention

Presence of TERT promoter mutations

Comparator

Absence of TERT promoter mutations or presence of ATRX/DAXX mutations

Outcomes

Frequency of TERT promoter mutations across tumor types, mutual exclusivity with ATRX mutations, association with tissues of low self-renewal

Design

Type

Cross-sectional molecular survey

Randomized

No

Multicenter

Yes

Blinded

Not applicable: molecular analysis

Follow-up

None: cross-sectional design

Primary endpoint

Frequency of TERT promoter mutations across 60 tumor types

Secondary endpoints

  • Mutual exclusivity between TERT and ATRX mutations
  • Association with tissue self-renewal rates

Practice impact

What this means

This molecular survey of 1,230 tumors found TERT promoter mutations in 83% of primary glioblastomas, defining a TERT-high group of tumors from tissues with low self-renewal. TERT and ATRX mutations were mutually exclusive, suggesting alternative telomere maintenance pathways. These mutations are now used as biomarkers for glioma classification.

Bottom line

TERT promoter mutations are highly prevalent in primary glioblastoma (83%) and mutually exclusive with ATRX mutations, supporting their role as a diagnostic biomarker.

Strength of evidence

moderate

Recommendation

consider change

Why it matters

  • High frequency in glioblastoma provides strong diagnostic signal
  • Mutual exclusivity with ATRX aids in molecular classification
  • Cross-sectional design limits causal inference

What would change my mind

  • Prospective validation of TERT mutation impact on survival
  • Randomized trials of TERT-targeted therapies
  • Replication in independent, population-based cohorts

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

Low for mutation detection; potential selection bias in tumor sample collection

Confounding

Tumor heterogeneity and sample size variation across types not fully addressed

Missing data

Not reported; likely minimal for mutation status

Multiplicity

Multiple comparisons across 60 tumor types without correction

Notes

  • Large sample size (1,230 tumors)
  • Multiple contributing centers

Stats check

NNT

N/A

Effect sizes

  • 83% of primary glioblastomas had TERT promoter mutations
  • TERT-high defined as ≥15% frequency

Absolute effects

  • 1,230 tumors surveyed
  • 9 tumor types classified as TERT-high

Concerns

  • No confidence intervals reported for mutation frequencies
  • Descriptive statistics only

External validity

Who it applies to

Patients with gliomas, especially primary glioblastoma, and other TERT-high tumors (melanomas, liposarcomas, etc.)

Who it does not

Tumors from tissues with high self-renewal rates (e.g., colon, breast)

Generalizability notes

  • Based on diverse tumor bank samples
  • Findings specific to mutation prevalence, not clinical outcomes

Evidence trace

Source trace and metadata

Citations (3)

claim_id

methods_critique.risk_of_bias

locator

p. 1 Results

quote

we surveyed 1,230 tumors of 60 different types

claim_id

stats_check.effect_sizes

locator

p. 1 Results

quote

including 83% of primary glioblastoma

claim_id

practice_impact.bottom_line

locator

p. 1 Results

quote

TERT and ATRX mutations were mutually exclusive

Metadata

Generated at

2026-03-06T13:41:29.251Z

Version

top 100 cited in past 20 years