Clinicopathological and molecular characteristics of papillary thyroid carcinoma with BRAF V600E and TERT promoter co-mutations
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View abstract on PubMed
Summary
This summary is machine-generated.BRAF V600E and TERT promoter co-mutations in thyroid cancer are linked to worse outcomes and resistance to radioactive iodine therapy. These co-mutations impact thyroid hormone synthesis pathways, contributing to disease progression.
Area Of Science
- Endocrinology
- Oncology
- Molecular Biology
Background
- BRAF V600E and TERT promoter co-mutations are prevalent in thyroid cancer.
- These co-mutations are associated with poorer patient prognosis.
Purpose Of The Study
- Investigate the relationship between BRAF V600E and TERT promoter co-mutations and clinicopathological features in papillary thyroid cancer (PTC).
- Identify molecular pathways affected by these co-mutations.
Main Methods
- Utilized customized mutation detection panels for multiplex PCR and gene sequencing on 73 PTC tumor samples.
- Analyzed TCGA thyroid cancer data for clinical correlations, differential gene expression, and Weighted Gene Co-expression Network Analysis (WGCNA).
- Performed gene ontology and KEGG pathway enrichment analysis on overlapping differentially expressed genes.
Main Results
- BRAF V600E and TERT C228T co-mutations occurred in 10.96% of PTC patients.
- Co-mutated patients exhibited older onset age, higher MACIS scores, larger tumors, and resistance to radioactive iodine therapy.
- Survival analysis revealed poorer overall and progression-free survival in co-mutated patients. Downregulation of 10 thyroid hormone synthesis-related genes was observed.
Conclusions
- BRAF V600E and TERT promoter co-mutations contribute to thyroid cancer progression and poor prognosis.
- Downregulation of thyroid hormone synthesis genes, including iodide transporters and biosynthesis genes, may drive radioactive iodine therapy resistance in co-mutated PTC.
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