Which gene is inactivated in retinoblastoma, and what is its chromosomal location?

Explanation

## RB1 Gene and Retinoblastoma **Key Point:** The RB1 (retinoblastoma) gene located on chromosome 13q14 is the causative gene in retinoblastoma. Inactivation of both alleles ("two-hit" hypothesis) leads to malignant transformation of retinal cells. ### Mechanism of Tumorigenesis **High-Yield:** The RB1 gene encodes the retinoblastoma protein (pRb), which acts as a tumor suppressor by: - Controlling G1/S cell cycle checkpoint - Binding and inactivating E2F transcription factors - Preventing uncontrolled cell proliferation When both copies are inactivated, cells lose this critical brake on division, leading to retinoblastoma development. ### Two-Hit Hypothesis 1. **Hereditary form:** First mutation inherited in germline; second mutation acquired somatically in retinal cells 2. **Sporadic form:** Both mutations acquired somatically (rare, usually unilateral) **Clinical Pearl:** Bilateral retinoblastoma is virtually always hereditary and indicates germline RB1 mutation. ### Associated Syndromes - **Hereditary retinoblastoma:** 40% of cases; 90% bilateral or multifocal - **Trilateral retinoblastoma:** Retinoblastoma + pineal gland tumor (pineoblastoma) in RB1 germline carriers - **Increased cancer risk:** RB1 germline carriers have elevated lifetime risk of secondary malignancies (sarcomas, lung cancer, melanoma) **Mnemonic:** **RB13** — RB gene on chromosome **13**