Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers (original) (raw)

Nature volume 368, pages 753–756 (1994)Cite this article

Abstract

CYTOGENETIC abnormalities of chromosome 9p21 are characteristic of malignant melanomas1,2, gliomas3, lung cancers4 and leukaemias5. From a panel of 46 human malignant cell lines, we localized by positional cloning the most frequently deleted region on 9p21. Sequence analysis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cyclin-dependent kinase 4 (CDK4) 6. Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. One carcinoma had a deletion entirely within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0663, USA
    Tsutomu Nobori, Kaoru Miura, David J. Wu, Augusto Lois & Dennis A. Carson
  2. CIBA-GEIGY Pharmaceuticals Division, CH-4002, Basel, Switzerland
    Kenji Takabayashi

Authors

  1. Tsutomu Nobori
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  2. Kaoru Miura
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  3. David J. Wu
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  4. Augusto Lois
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  5. Kenji Takabayashi
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  6. Dennis A. Carson
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Nobori, T., Miura, K., Wu, D. et al. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers.Nature 368, 753–756 (1994). https://doi.org/10.1038/368753a0

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