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A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

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Abstract

The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells1–4. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles5–7. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes8. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb (refs 9–12), assigned to the q14 band of human chromosome 13 (refs 13–22). Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours23, almost half of which are osteosarcomas believed to be caused by the same mutation24,25. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13ql4, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, 02142, USA

    Stephen H. Friend, Rene Bernards, Snezna Rogelj & Robert A. Weinberg

  2. Division of Hematology-Oncology, The Children's Hospital, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Stephen H. Friend

  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Robert A. Weinberg

  4. Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, Massachusetts, 02114, USA

    Joyce M. Rapaport, Daniel M. Albert & Thaddeus P. Dryja

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  1. Stephen H. Friend
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  2. Rene Bernards
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  3. Snezna Rogelj
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  4. Robert A. Weinberg
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  5. Joyce M. Rapaport
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  6. Daniel M. Albert
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  7. Thaddeus P. Dryja
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Friend, S., Bernards, R., Rogelj, S. et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643–646 (1986). https://doi.org/10.1038/323643a0

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  • DOI: https://doi.org/10.1038/323643a0

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