A 58-year-old man with small cell lung carcinoma develops hyponatremia unresponsive to fluid restriction. Which molecular mechanism best explains the ectopic hormone production responsible for this syndrome?
- A Demethylation of the CpG island in the AVP gene promoter activating transcription in neuroendocrine tumor cells ✓
- B Amplification of the MYC oncogene driving transcription of the vasopressin gene
- C Loss of SSTR2 receptor expression leading to unregulated somatostatin signalling
- D Gain-of-function mutation in the V2 receptor preventing ectopic vasopressin clearance
Correct answer: A. Demethylation of the CpG island in the AVP gene promoter activating transcription in neuroendocrine tumor cells
Explanation
Small cell lung carcinoma, a high-grade neuroendocrine tumor, produces ectopic ADH (SIADH) via epigenetic derepression: hypomethylation of CpG islands at the AVP gene promoter allows transcriptional activation in non-hypothalamic cells. MYC amplification drives general proliferation but is not the specific mechanism for AVP transcription; SSTR2 loss relates to somatostatin insensitivity; V2 receptor mutations affect nephrogenic DI, not ectopic production.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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