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...
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American Society of Clinical Oncology
2025-07-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO-24-00610 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vaishakhi Trivedi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1270f8624b4641a1a6b2f9b26c19e948 |
| institution | DOAJ |
| issn | 2687-8941 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | American Society of Clinical Oncology |
| record_format | Article |
| series | JCO Global Oncology |
| spelling | doaj-art-1270f8624b4641a1a6b2f9b26c19e9482025-08-20T02:39:50ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412025-07-011110.1200/GO-24-00610Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular PlasticityVaishakhi Trivedi0Vanita Noronha1Munita Bal2Pratik Chandrani3Disha Poojary4Elveera Saldanha5Anuradha Choughule6Priyanka Pange7Vinod Gupta8Nandini Menon9Vijay Patil10Minit Shah11Pankaj Chaturvedi12Kumar Prabhash13Amit Dutt14Department of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Pathology, Tata Memorial Hospital, Mumbai, IndiaHomi Bhabha National Institute, Training School Complex, Mumbai, IndiaMedical Oncology Molecular Laboratory, Tata Memorial Hospital, Mumbai, IndiaHomi Bhabha National Institute, Training School Complex, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaHomi Bhabha National Institute, Training School Complex, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaIntegrated Cancer Genomics Laboratory, Department of Genetics (Biotech Centre), University of Delhi South Campus, New Delhi, IndiaPURPOSELineage-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.https://ascopubs.org/doi/10.1200/GO-24-00610 |
| spellingShingle | 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 Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity JCO Global Oncology |
| title | Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity |
| title_full | Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity |
| title_fullStr | Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity |
| title_full_unstemmed | Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity |
| title_short | Comprehensive Genomic Profiling of Anaplastic Thyroid Cancer Identifies Alterations in THRA, a Potential Modifier of Cellular Plasticity |
| title_sort | comprehensive genomic profiling of anaplastic thyroid cancer identifies alterations in thra a potential modifier of cellular plasticity |
| url | https://ascopubs.org/doi/10.1200/GO-24-00610 |
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