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

A. Hogg, B. Bia, Z. Onadim, John Kenneth Cowell

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84 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7351-7355
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number15
DOIs
StatePublished - Jan 1 1993

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Retinoblastoma
Point Mutation
Mutation
Terminator Codon
Exons
Neoplasms
Sequence Deletion
Nucleic Acid Repetitive Sequences
Loss of Heterozygosity
Germ Cells
Codon
Arginine
Reading
Carcinogenesis
Alleles
Genes

ASJC Scopus subject areas

  • General

Cite this

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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.",
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AU - Bia, B.

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N2 - 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.

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