Mutations in the retinoblastoma gene and their expression in somatic and tumor cells of patients with hereditary retinoblastoma
- 1 January 1994
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 3 (1), 44-51
- https://doi.org/10.1002/humu.1380030108
Abstract
Two intragenic deletions (exon 18–19 and exon 24) and two point mutations (one missense mutation in exon 21 and one mutation at splice-donor site for exon 13) were detected in the retinoblastoma gene in somatic and tumor cells of patients with hereditary retinoblastoma. Three mutations were located in a domain essential for binding to oncoproteins encoded by DNA tumor viruses (Hu et al., 1990; Huang et al., 1990). One mutation (deletion of exon 24) was outside this domain but it is in the region essential for binding to transcriptional factor E2F, and for suppression of malignant phenotypes (Qian et al., 1992; Qin et al., 1992). A minisatellite-like sequence and short repeated sequences were located at the breakpoint of the deletion of exon 24, suggesting that two deletions on both sides of the minisatellite-like sequence may be generated by a “DNA slippage and misalignment” mechanism. Upon amplification of cDNA by the polymerase chain reaction, no transcript of gene with frameshift mutation (deletion of exon 24) was detected in skin fibroblasts, while transcripts of genes with missense mutations were detected. The results, in combination with previous reports (Dunn et al., 1989; Hashimoto et al., 1991), suggest the instability of transcripts with a premature stop codon or the suppressed expression of alleles with a premature stop codon in the retinoblastoma gene in somatic cells of hereditary patients.Keywords
This publication has 30 references indexed in Scilit:
- The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding proteinCell, 1991
- The E2F transcription factor is a cellular target for the RB proteinCell, 1991
- The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2FCell, 1991
- Mutations in the RB1 gene and their effects on transcription.Molecular and Cellular Biology, 1989
- Short, direct repeats at the breakpoints of deletions of the retinoblastoma gene.Proceedings of the National Academy of Sciences, 1989
- Human retinoblastoma gene: long-range mapping and analysis of its deletion in a breast cancer cell line.Molecular and Cellular Biology, 1989
- Identification of Germline and Somatic Mutations Affecting the Retinoblastoma GeneScience, 1988
- Types, rates, origin and expressivity of chromosome mutations involving 13q14 in retinoblastoma patientsHuman Genetics, 1988
- Nonsense mutations in the human beta-globin gene affect mRNA metabolism.Proceedings of the National Academy of Sciences, 1988
- Premature translation termination mediates triosephosphate isomerase mRNA degradation.Molecular and Cellular Biology, 1988