Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79
- Univ. of California, San Diego, La Jolla (USA)
Formation of retinoblastoma, a cancer arising in the retinas of young children, is determined by mutational inactivation of an autosomal gene (RB), which has been molecularly cloned. Whereas all normal tissues and many tumor cells express an RB mRNA of 4.7 kilobases, six of six retinoblastomas were previously found either to lack RB gene expression or to have RB transcripts of abnormal (reduced) length. To further characterize the latter type of mutation, the authors chose to examine retinoblastoma cell line Y79, which expressed a shortened RB mRNA of about 4.0 kilobases. RB cDNA clones isolated from a library constructed with Y79 mRNA demonstrated an internal loss of 470 nucleotides near the 5{prime} end, which corresponded to a deletion of exons 2-6. Genomic clones containing the deletion junction were isolated from a library made with Y79 DNA, which allowed precise localization and sequencing of deletion endpoints in introns 1 and 6. These regions had no apparent homology to each other or to the Alu family of repetitive sequences, implying that the deletion must have occurred by a mechanism other than recombination of homologous sequences. Deletion of exons 2-6 would interrupt the open reading frame in RB mRNA and would result in premature termination of translation. Since no normal RB protein was detected by immunoprecipitation with specific antibody, the other, apparently normal RB allele in Y79 cells was necessarily inactivated by a different mutation.
- OSTI ID:
- 5517441
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:16; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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DNA SEQUENCING
MESSENGER-RNA
NEOPLASMS
PHOSPHORUS 32
RETINA
TRANSCRIPTION
TUMOR CELLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGY
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DAYS LIVING RADIOISOTOPES
DISEASES
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LIGHT NUCLEI
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NUCLEIC ACIDS
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ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS ISOTOPES
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STRUCTURAL CHEMICAL ANALYSIS
550201* - Biochemistry- Tracer Techniques