Which of the following epigenetic mechanisms is PRIMARILY responsible for silencing of tumour suppressor genes in cancer, without altering the underlying DNA sequence?

• A Global genomic hypermethylation causing chromatin compaction
• B Histone H4 acetylation at lysine residues
• C Demethylation of satellite DNA repeats
• D Hypermethylation of CpG islands in promoter regions ✓

Explanation

Cancer cells characteristically show hypermethylation of CpG islands in the promoter regions of tumour suppressor genes (e.g., RB1, CDKN2A/p16, BRCA1), silencing their transcription without mutating the gene. Paradoxically, the overall genome is globally hypomethylated in cancer, which contributes to genomic instability; satellite repeat demethylation reflects this global hypomethylation, which activates rather than silences genes.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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