title: Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma.
abstract: 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.
authors.affiliation: Imperial Cancer Research Fund, Institute of Child Health, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Hogg
authors.forename: B
authors.initials: B
authors.lastname: Bia
authors.forename: Z
authors.initials: Z
authors.lastname: Onadim
authors.forename: J K
authors.initials: JK
authors.lastname: Cowell
mesh_terms: D001483:Base Sequence; D003062:Codon; D016161:Genes, Retinoblastoma; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017354:Point Mutation; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D012175:Retinoblastoma / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D003062:Codon; D009838:Oligodeoxyribonucleotides