Tumor Suppressors—Retinoblastoma Genetics Retinoblastoma in children most commonly results from mutation in which class of gene?

Introduction / Context:
Retinoblastoma is a pediatric eye tumor that provided the classic model for tumor suppressor gene function and the “two-hit hypothesis.” The RB1 gene encodes the retinoblastoma protein (pRB), a negative regulator of the G1→S transition in the cell cycle. This item asks you to identify the gene class most directly implicated in retinoblastoma pathogenesis.

Given Data / Assumptions:

• RB1 loss leads to uncontrolled E2F activity and cell-cycle progression.
• Hereditary cases inherit one mutant RB1 allele and acquire a second somatic hit.

Concept / Approach:
Decide whether the driver is activation of an oncogene or loss of a tumor suppressor. Retinoblastoma arises from biallelic inactivation of RB1, making it the prototypical tumor suppressor gene–driven cancer.

Step-by-Step Solution:

Verification / Alternative check:
Knudson’s two-hit model was formulated from bilateral vs unilateral retinoblastoma data, consistent with tumor suppressor loss rather than oncogene activation alone.

Why Other Options Are Wrong:

• Kinase/cyclin activation are oncogene mechanisms but are not the hallmark initiating lesion in retinoblastoma.
• Oncogenic viruses are not the primary cause here.
• GPCR activation is not the canonical driver.

Common Pitfalls:
Confusing oncogene gain-of-function with tumor suppressor loss-of-function; forgetting the two-hit requirement.

Final Answer:
Tumor suppressor (loss of RB1 function)