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Title: Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79

Abstract

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 inmore » 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.« less

Authors:
; ; ; ; ;  [1]
  1. Univ. of California, San Diego, La Jolla (USA)
Publication Date:
OSTI Identifier:
5517441
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America; (USA)
Additional Journal Information:
Journal Volume: 85:16; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARCINOGENESIS; GENETICS; GENES; INACTIVATION; RECOMBINANT DNA; DNA SEQUENCING; MESSENGER-RNA; NEOPLASMS; PHOSPHORUS 32; RETINA; TRANSCRIPTION; TUMOR CELLS; ANIMAL CELLS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGY; BODY; BODY AREAS; DAYS LIVING RADIOISOTOPES; DISEASES; DNA; EYES; FACE; HEAD; ISOTOPES; LIGHT NUCLEI; NUCLEI; NUCLEIC ACIDS; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANS; PATHOGENESIS; PHOSPHORUS ISOTOPES; RADIOISOTOPES; RNA; SENSE ORGANS; STRUCTURAL CHEMICAL ANALYSIS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Lee, E Y.H.P., Bookstein, R, Young, Lihjiuan, Lin, Chijen, Rosenfeld, M G, and Lee, Wenhwa. Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79. United States: N. p., 1988. Web. doi:10.1073/pnas.85.16.6017.
Lee, E Y.H.P., Bookstein, R, Young, Lihjiuan, Lin, Chijen, Rosenfeld, M G, & Lee, Wenhwa. Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79. United States. https://doi.org/10.1073/pnas.85.16.6017
Lee, E Y.H.P., Bookstein, R, Young, Lihjiuan, Lin, Chijen, Rosenfeld, M G, and Lee, Wenhwa. 1988. "Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79". United States. https://doi.org/10.1073/pnas.85.16.6017.
@article{osti_5517441,
title = {Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79},
author = {Lee, E Y.H.P. and Bookstein, R and Young, Lihjiuan and Lin, Chijen and Rosenfeld, M G and Lee, Wenhwa},
abstractNote = {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.},
doi = {10.1073/pnas.85.16.6017},
url = {https://www.osti.gov/biblio/5517441}, journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
issn = {0027-8424},
number = ,
volume = 85:16,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 1988},
month = {Mon Aug 01 00:00:00 EDT 1988}
}