All are true regarding retinoblastoma except:
Rb gene aka "Governor of the cell cycle" is a key negative regulator of the G1/S cell cycle transition. Rb gene is located on 13q14 chromosome. To explain the two patterns of occurrence of retinoblastoma, Knudson proposed his now canonic "two hit" hypothesis of oncogenesis. Two mutations (hits), involving both alleles of RB at chromosome locus 13q14, are required to produce retinoblastoma. In familial Retinoblastoma cases, children inherit one defective copy of the RB gene in the germline (the first hit), and the other copy is normal. Retinoblastoma develops when the normal RB allele is mutated in retinoblasts as a result of a spontaneous somatic mutation (the second hit). Because such second hits seem to be viually inevitable in a small fraction of retinoblasts, most individuals inheriting a germline defect in one RB allele develop unilateral or bilateral retinoblastoma, and the disease is inherited as an autosomal dominant trait. In sporadic Retinoblastoma cases both normal RB alleles must undergo somatic mutation in the same retinoblast (two hits). The probability of this event is low (explaining why retinoblastoma is an uncommon tumor in the general population), but the end result is the same: a retinal cell that has completely lost RB function and becomes cancerous. Inhibitors of Cell Cycle Progression RB Retinoblastoma (RB) protein Inhibitor of G1/S transition during cell cycle progression Familial retinoblastoma syndrome (retinoblastoma, osteosarcoma, other sarcomas) Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung CDKN2A p16/INK4a and p14/ARF P16: Negative regulator of cyclin-dependent kinases; p14, indirect activator of p53 Familial melanoma Pancreatic, breast and esophageal carcinoma melanoma, ceain leukemias
They play major role in cell cycle regulation
Require deletion of both the Rb genes
Familial variant is autosomal dominant in inheritance
Chromosome 13p 14
JIPMER 2017