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

Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7351-5. doi: 10.1073/pnas.90.15.7351.


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.

MeSH terms

  • Base Sequence
  • Codon
  • Genes, Retinoblastoma*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Oligodeoxyribonucleotides / chemistry
  • Point Mutation
  • RNA Splicing
  • Repetitive Sequences, Nucleic Acid
  • Retinoblastoma / genetics*
  • Sequence Deletion


  • Codon
  • Oligodeoxyribonucleotides