JCO global oncology · 2025
Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity.
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Trivedi Vaishakhi, Noronha Vanita, Bal Munita, Chandrani Pratik, Poojary Disha, Saldanha Elveera, Choughule Anuradha, Pange Priyanka, Gupta Vinod, Menon Nandini, Patil Vijay, Shah Minit, Chaturvedi Pankaj, Prabhash Kumar, Dutt Amit
Аннотация
PURPOSE: Lineage-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 METHODS: We performed whole-exome sequencing and targeted sequencing of 68 formalin-fixed paraffin-embedded orphan tumors of ATC from Indian patients.
RESULTS: Our 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.
CONCLUSION: Our data reveal the significant association of THRA mutations potentially influencing cellular plasticity in a subset of patients with ATC.
MATERIALS AND METHODS: We performed whole-exome sequencing and targeted sequencing of 68 formalin-fixed paraffin-embedded orphan tumors of ATC from Indian patients.
RESULTS: Our 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.
CONCLUSION: Our data reveal the significant association of THRA mutations potentially influencing cellular plasticity in a subset of patients with ATC.