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Published on: June 7, 2019
BRAF Mutation Affects Intratumor Heterogeneity in Papillary Thyroid Carcinoma.
1Ultrasound Nursing, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China, z2hospital.com.
Analytical Cellular Pathology (Amsterdam)
|May 18, 2026
Summary
Intratumor heterogeneity (ITH) impacts papillary thyroid cancer patient outcomes, particularly disease-free interval. Thyroid differentiation score (TDS) and BRAF mutation influence ITH, with TDS suppressing BRAF’s effect.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Intratumor heterogeneity (ITH) significantly impacts patient prognosis.
- The role of ITH and its drivers in papillary thyroid carcinoma (PTC) remains incompletely understood.
- Further investigation is warranted to clarify ITH's prognostic value and influencing factors in PTC.
Purpose of the Study:
- To assess the prognostic impact of ITH on clinical outcomes in papillary thyroid carcinoma (PTC).
- To identify key factors influencing ITH in PTC.
- To explore pathways associated with ITH in PTC.
Main Methods:
- Utilized The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort data, including Mutation Annotation Format (MAF) and clinical features.
- Quantified ITH using the Mutant Allele Tumor Heterogeneity (MATH) score.
- Performed regression, subgroup, and mediation analyses to identify ITH drivers and their interactions.
Main Results:
- Higher ITH was significantly associated with a poorer disease-free interval (DFI) in PTC patients (HR=2.64, p=0.01).
- Thyroid differentiation score (TDS) and BRAF mutation were identified as independent factors influencing ITH.
- TDS demonstrated a suppressive effect on the impact of BRAF mutation on ITH, and propionate metabolism was the most associated pathway.
Conclusions:
- ITH is a significant prognostic factor for DFI in PTC patients.
- TDS and BRAF mutation are key determinants of ITH in PTC.
- TDS modulates the influence of BRAF mutation on ITH, highlighting complex regulatory mechanisms.
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