Retinoblastoma is most commonly associated with mutation in which gene and inheritance pattern?

• A. RB1 gene; autosomal dominant
• B. RB1 gene; autosomal recessive
• C. p53 gene; autosomal dominant
• D. RB2 gene; X-linked

Answer: (A)

Mutation in RB1, the gene encoding the retinoblastoma protein, is the classic driver of this tumor. The RB1 protein is a key brake on the cell cycle, keeping cells from progressing from G1 to S phase. When RB1 is inactivated, a second somatic event in a retinal cell can remove the remaining brake, allowing uncontrolled division and tumor formation. The heritable form carries a germline RB1 mutation, so one defective allele is present in all cells; tumor development then follows the two-hit mechanism, with a second hit in retinal tissue. This explains why the heritable form often presents with bilateral, multifocal tumors at a younger age, while sporadic cases are usually unilateral and occur later. RB1 is the primary gene involved; p53 is not the usual driver for retinoblastoma, and RB2 is not the standard associated gene.