Evidence map›Paper›PMID 41701943›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026

DNA Methylation-Based Risk Stratification and Classification of Pediatric Thyroid Carcinoma.

Jenny Z Li, Julio C Ricarte-Filho, Amber R Isaza, Kyle Hinkle, Feng Xu, Marilyn M Li, Andrew J Bauer, Aime T Franco, Wanding Zhou

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Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jenny Z Li *Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0009-0004-9990-2350
Julio C Ricarte-Filho *The Thyroid Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0002-8427-6869
Amber R IsazaThe Thyroid Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0003-0863-7500
Kyle HinkleThe Thyroid Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0009-0005-7937-1246
Feng XuGenomic Diagnostic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0002-7227-7426
Marilyn M LiGenomic Diagnostic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0002-4253-2369
Andrew J BauerThe Thyroid Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0002-3952-881X
Aime T FrancoThe Thyroid Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0002-1677-5228
Wanding ZhouCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0001-9126-1932

Funding

RESEARCH AND MENTORING EXCELLENCE IN DIVERSE AND INCLUSIVE ENVIRONMENTR01CA214511 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI FRANCO, AIME T. · 2018 to 2023
$2.7M
Decoding Single-cell DNA Methylomes for Epigenetic Cell IdentityR35GM146978 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI Wanding Zhou · 2022 to 2026
$2.2M
National Cancer Institute (NCI) R01-CA214511National Institute of General Medical Sciences (NIGMS) R35-GM146978NCI NIH HHS R01 CA214511NIGMS NIH HHS R35 GM146978U.S. Department of Defense (DOD) W81XWH2210655
6 · The paper itself

Abstract

purposeAccurate assessment of invasiveness in pediatric thyroid carcinomas is essential to prevent unnecessary surgery and avoid surgery-associated complications. DNA methylation, a proven molecular biomarker for cancer classification, holds promise for stratifying thyroid cancer risk. The objectives were to determine the epigenetic hallmarks of pediatric thyroid carcinomas and investigate whether DNA methylome profiling is a feasible approach for preoperative risk stratification of this pediatric disease. EXPERIMENTAL

designWe interrogated genome-wide DNA methylation profiles from two separately processed cohorts of pediatric thyroid carcinoma. The reference cohort included 100 samples, consisting of 87 well-differentiated primary tumors-77 papillary and 10 follicular thyroid carcinomas-and 13 matched lymph node metastases. To predict oncogenic drivers and tumor invasiveness, defined by the presence of nodal metastasis, we trained two classifiers on the reference cohort and then evaluated their performance on a second validation cohort of 84 samples, including 83 primary tumors and one lymph node metastasis.

resultsWe identified distinct methylation patterns associated with tumor invasiveness and key driver mutations, including BRAF p.V600E, RAS-like mutations, kinase fusions, and DICER1 mutations. The differentially methylated regions reflect inflammatory stress and disrupted thyroid development and function, implicating androgen receptor, Hippo, and AP-1 signaling. Leveraging these epigenetic signatures, we developed and validated two methylation-based classifiers that accurately predict tumor invasiveness and oncogenic mutation subgroups.

conclusionsIn patients with pediatric thyroid carcinoma, DNA methylation assays accurately predict tumor invasiveness and driver mutations. Our findings highlight the clinical value of DNA methylation profiling for risk stratification and classification of pediatric thyroid cancers.

Indexed as

Adenocarcinoma, FollicularBiomarkers, TumorDNA MethylationThyroid NeoplasmsAdolescentCarcinoma, PapillaryChildChild, PreschoolEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMaleMutationProto-Oncogene Proteins B-rafBiomarkers, TumorProto-Oncogene Proteins B-raf

Identifiers

PMID41701943
PMCPMC13059138

What Socratic holds

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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 Socratic graph.