title: Deletions and rearrangements inactivate the p16INK4 gene in human glioma cells.
abstract: Structural alterations in the p16INK4 gene were examined in early passage human glioma cell lines and related to the expression of p16 transcripts and protein. Using the Southern blot approach, we observed both homozygous and hemizygous deletions, as well as rearrangements of the p16 and p15 genes in 5 of the 7 cell lines (71%). Two cell lines, MGR3 and HBT28, revealed hemizygous deletion of the p16 and p15 genes combined with indistinguishable rearrangements of the remaining p15-p16 locus that resulted in loss of exon 2 sequences for p15 and p16, but retention of p16 exon 1; neither of these cell lines expressed p16 mRNA. Data for a third cell line, MGR2, indicated a similar, but unique rearrangement involving the p15 and p16 genes. MGR2, which retained a single wild-type p15-p16 locus, showed expression of p16 transcript, but not of p16 protein as indicated by Western blot analysis. All the glioma cell lines expressed similar levels of the retinoblastoma protein and no amplification of the cyclin-dependent kinase 4 gene. These results demonstrate that human glioma cells contain p16 gene microdeletions and rearrangements that contribute to inactivation of the cell cycle regulatory protein.
authors.affiliation: Department of Experimental Pediatrics, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Srivenugopal
authors.forename: F
authors.initials: F
authors.lastname: Ali-Osman
mesh_terms: D015139:Blotting, Southern; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017353:Gene Deletion; D015321:Gene Rearrangement; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger