Evidence map›Paper›PMID 25024077›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014

BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence.

Mingzhao Xing, Rengyun Liu, Xiaoli Liu, Avaniyapuram Kannan Murugan, Guangwu Zhu, Martha A Zeiger, Sara Pai, Justin Bishop

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 371 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
371citing papers in PubMed, 3 pooled it
44.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

371 citing papers in PubMed, 3 syntheses or guidelines pooled it, 703 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Enhancing Radioiodine Incorporation inThyroid : official journal of the American Thyroid Association · 2022
    Trial
  5. Cytologic and Surgical Correlation ofInternational journal of surgical pathology · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026
    Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

311 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Mingzhao XingAll authors: Johns Hopkins University School of Medicine, Baltimore, MD. mxing1@jhmi.edu.
Rengyun LiuAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Xiaoli LiuAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Avaniyapuram Kannan MuruganAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Guangwu ZhuAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Martha A ZeigerAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Sara PaiAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Justin BishopAll authors: Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins University · US

Funding

Genetic & Epigenetic Events in Papillary Thyroid CancerR01CA113507 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2006 to 2015
$2.2M
Molecular Events in the PI3K/Akt Pathway in Thyroid CancerR01CA134225 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2009 to 2013
$1.6M
NCI NIH HHS R01 CA113507NCI NIH HHS R01CA113507NCI NIH HHS R01 CA134225NCI NIH HHS R01CA134225
6 · The paper itself

Abstract

purposeTo investigate the prognostic value of the BRAF V600E mutation and the recently identified TERT promoter mutation chr5:1,295,228C>T (C228T), individually and in their coexistence, in papillary thyroid cancer (PTC). PATIENTS AND

methodsWe performed a retrospective study of the relationship of BRAF and TERT C228T mutations with clinicopathologic outcomes of PTC in 507 patients (365 women and 142 men) age 45.9 ± 14.0 years (mean ± SD) with a median follow-up of 24 months (interquartile range, 8 to 78 months).

resultsCoexisting BRAF V600E and TERT C228T mutations were more commonly associated with high-risk clinicopathologic characteristics of PTC than they were individually. Tumor recurrence rates were 25.8% (50 of 194;77.60 recurrences per 1,000 person-years; 95% CI, 58.81 to 102.38) versus 9.6% (30 of 313; 22.88 recurrences per 1,000 person-years; 95% CI, 16.00 to 32.72) in BRAF mutation-positive versus -negative patients (hazard ratio [HR], 3.22; 95% CI, 2.05 to 5.07) and 47.5% (29 of 61; 108.55 recurrences per 1,000 person-years; 95% CI, 75.43 to 156.20) versus 11.4% (51 of 446; 30.21 recurrences per 1,000 person-years; 95% CI, 22.96 to 39.74) in TERT mutation-positive versus -negative patients (HR, 3.46; 95% CI, 2.19 to 5.45). Recurrence rates were 68.6% (24 of 35; 211.76 recurrences per 1,000 person-years; 95% CI, 141.94 to 315.94) versus 8.7% (25 of 287; 21.60 recurrences per 1,000 person-years; 95% CI, 14.59 to 31.97) in patients harboring both mutations versus patients harboring neither mutation (HR, 8.51; 95% CI, 4.84 to 14.97), which remained significant after clinicopathologic cofactor adjustments. Disease-free patient survival curves displayed a moderate decline with BRAF V600E or TERT C228T alone but a sharp decline with two coexisting mutations.

conclusionCoexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines PTC with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications.

Indexed as

MutationCarcinomaCarcinoma, PapillaryDisease-Free SurvivalFemaleHumansMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisPromoter Regions, GeneticProto-Oncogene Proteins B-rafRetrospective StudiesTelomeraseThyroid Cancer, PapillaryThyroid NeoplasmsBRAF protein, humanProto-Oncogene Proteins B-rafTelomeraseTERT protein, human

Identifiers

PMID25024077
PMCPMC4145183
OpenAlexW2102146456

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.