Distantly metastatic differentiated thyroid carcinoma is kinase-driven and enriched for DNA repair and DNA methylation gene alterations - PubMed
3 hours ago
- #DNA repair
- #thyroid carcinoma
- #methylation
- Distantly metastatic differentiated thyroid carcinoma (DMDTC) is kinase-driven and enriched for DNA repair and DNA methylation gene alterations.
- DMDTC is the leading cause of thyroid cancer-related mortality despite being uncommon.
- Genetic alterations in DMDTC involve phosphorylation signaling pathways, DNA damage repair (DDR)-related genes, and genome-wide methylation dysregulation.
- Novel fusions (SPON1::ALK, RFTN1::BRAF) and mutations (PTEN, STK11, DNMT3A) enhance downstream phosphorylation levels and induce methylation dysregulation.
- DMDTCs exhibit chromosomal instability and aberrant methylation, highlighting DDR gene-targeted therapy as a promising strategy.
- The study cohort included 78 patients with DMDTC, with lung and bone being the most common metastatic sites.
- Multiple metastases and older age were associated with worse metastasis-free and overall survival.