Telomerase reverse transcriptase (TERT) promoter mutations (C228T and C250T) are found in which of the following tumor types at the highest frequency (>70%)?

• A Glioblastoma IDH-wildtype
• B Papillary thyroid carcinoma
• C Hepatocellular carcinoma
• D Cutaneous melanoma ✓

Explanation

TERT promoter mutations (C228T and C250T) creating de novo ETS transcription factor binding sites are found at the highest frequency (~70–85%) in cutaneous melanoma, making them a hallmark of UV-induced mutagenesis in this tumor. These mutations lead to transcriptional upregulation of TERT, conferring replicative immortality. Glioblastoma IDH-wildtype has TERT promoter mutations in ~70% but this is predominantly in secondary contexts; papillary thyroid carcinoma shows these mutations infrequently (<10%), and HCC shows them in ~50% of cases — all lower than cutaneous melanoma.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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