Which of the following best explains why tumor cells with mutated RAS oncogene have constitutive proliferative signalling even in the absence of growth factor receptor activation?
- A RAS mutation prevents GTP hydrolysis, locking RAS in the active GTP-bound state ✓
- B Mutant RAS blocks downstream RAF kinase phosphorylation permanently
- C RAS mutation increases affinity for GDP, amplifying receptor tyrosine kinase signalling
- D Mutant RAS directly activates p53 leading to apoptosis resistance
Correct answer: A. RAS mutation prevents GTP hydrolysis, locking RAS in the active GTP-bound state
Explanation
Normal RAS cycles between active GTP-bound and inactive GDP-bound forms; intrinsic GTPase activity hydrolyses GTP to GDP, terminating the signal. Point mutations at codons 12 or 13 of RAS impair GTPase activity, so RAS remains permanently GTP-bound and continuously activates downstream proliferative pathways (RAF/MEK/ERK). This accounts for the oncogenic gain-of-function phenotype seen in ~30% of all human cancers.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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