Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma.

The RB1 gene from 12 human retinoblastoma tumors has been analyzed exon-by-exon with the single-strand conformation polymorphism technique.
Mutations were found in all tumors, and one-third of the tumors had independent mutations in both alleles neither of which were found in the germ line, confirming their true sporadic nature.
In the remaining two-thirds of the tumors only one mutation was found, consistent with the loss-of-heterozygosity theory of tumorigenesis.
Point mutations, the majority of which were C-- > T transitions, were the most common abnormality and usually resulted in the conversion of an arginine codon to a stop codon.
Small deletions were the second most common abnormality and most often created a downstream stop codon as the result of a reading frameshift.
Deletions and point mutations also affected splice junctions.
Direct repeats were present at the breakpoint junctions in the majority of deletions, supporting a slipped-mispairing mechanism.
Point mutations generally produced DNA sequences which resulted in perfect homology with endogenous sequences which lay within 14 bp.. 
