TY - JOUR
T1 - Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma
AU - Hogg, Annette
AU - Bia, Britta
AU - Onadim, Zerrin
AU - Cowell, John K.
PY - 1993/8/1
Y1 - 1993/8/1
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.
AB - 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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M3 - Article
C2 - 8346255
AN - SCOPUS:0027297105
SN - 0027-8424
VL - 90
SP - 7351
EP - 7355
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -