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Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois 60637
Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS 1, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells.
1 The work was supported in part by J. S. McDonnell Foundation Grant 92-51 (O. I. O.), DOE Grant DE-FG02-86ER60408 (J. D. Rowley), and a training grant from the Deutsche Forschungsgemeinschaft (M. H. D.).
2 To whom requests for reprints should be addressed, at the Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland, Box 2115, Chicago, IL 60637.
Received 1/ 3/95. Accepted 1/24/95.
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