Detection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization.
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 I, 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.
Dreyling
M H
MH
Department of Medicine, University of Chicago, Illinois 60637.
Bohlander
S K
SK
Adeyanju
M O
MO
Olopade
O I
OI
D001932:Brain Neoplasms / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D002899:Chromosomes, Human, Pair 9; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics; D008545:Melanoma / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases