Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity

Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity

PURPOSELineage-specific cellular plasticity is one of the emerging hallmarks of cancer. The undifferentiated state of anaplastic thyroid cancer (ATC) represents an instance of cellular plasticity where lineage-specific molecular markers are underacknowledged. In this study, we identified recurrent m...

Full description

Saved in:
Bibliographic Details
Main Authors: Vaishakhi Trivedi, Vanita Noronha, Munita Bal, Pratik Chandrani, Disha Poojary, Elveera Saldanha, Anuradha Choughule, Priyanka Pange, Vinod Gupta, Nandini Menon, Vijay Patil, Minit Shah, Pankaj Chaturvedi, Kumar Prabhash, Amit Dutt
Format: Article
Language:English
Published: American Society of Clinical Oncology 2025-07-01
Series:JCO Global Oncology
Online Access:https://ascopubs.org/doi/10.1200/GO-24-00610
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:PURPOSELineage-specific cellular plasticity is one of the emerging hallmarks of cancer. The undifferentiated state of anaplastic thyroid cancer (ATC) represents an instance of cellular plasticity where lineage-specific molecular markers are underacknowledged. In this study, we identified recurrent mutations in the thyroid hormone receptor α (THRA) gene, which may play a role in lineage-specific cellular plasticity in ATC.MATERIALS AND METHODSWe performed whole-exome sequencing and targeted sequencing of 68 formalin-fixed paraffin-embedded orphan tumors of ATC from Indian patients.RESULTSOur analysis reveals the hallmark mutations in TP53 (approximately 42%), BRAF (approximately 10.3%), KRAS (approximately 2.9%), NRAS (29.4%), HRAS (23.5%), NF1 (1.5%), AKT1 (approximately 2.9%), and PIK3CA (approximately 1.5%) genes. Interestingly, we found significant mutations in THRA (approximately 11%) in our cohort, unlike the White population, which is a substantial gene in the thyroid cell's differentiation process. THRA mutations co-occur with TP53 and other hallmark genes, which suggests a synergetic molecular mechanism in phenotypic change in ATC.CONCLUSIONOur data reveal the significant association of THRA mutations potentially influencing cellular plasticity in a subset of patients with ATC.
ISSN:2687-8941

Similar Items