Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers

作者: Tsutomu Nobori , Kaoru Miura , David J. Wu , Augusto Lois , Kenji Takabayashi

DOI: 10.1038/368753A0

关键词: Dysplastic nevus syndromeNeoplastic transformationPositional cloningNonsense mutationCancer researchGeneComplementary DNAMolecular biologyCyclin-dependent kinase 4Southern blotBiology

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

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