Which of the following tumour suppressor gene mechanisms results in haploinsufficiency rather than requiring the classic two-hit hypothesis to promote tumorigenesis?

• A RB1 — single allele loss with no effect on cell cycle
• B APC — one functional copy fully suppresses Wnt signalling
• C PTEN — loss of one allele reduces PI3K signalling threshold, permitting premalignant growth ✓
• D VHL — heterozygous loss does not affect HIF stability

Explanation

PTEN is a classic haploinsufficient tumour suppressor; loss of one PTEN allele (monoallelic deletion or mutation) reduces PTEN protein levels sufficiently to elevate PIP3 and partially activate AKT signalling, promoting cell survival and proliferation even with one functioning allele remaining. RB1, APC, and VHL generally follow the classic two-hit model requiring biallelic inactivation before complete loss of suppressor function.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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