PMID- 11314047
OWN - NLM
STAT- MEDLINE
DCOM- 20010517
LR  - 20150204
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 20
IP  - 9
DP  - 2001 Mar 1
TI  - Quantitative real-time PCR does not show selective targeting of p14(ARF) but 
      concomitant inactivation of both p16(INK4A) and p14(ARF) in 105 human primary 
      gliomas.
PG  - 1103-9
AB  - In many human cancers, the INK4A locus is frequently mutated by homozygous 
      deletions. By alternative splicing this locus encodes two non-related tumor 
      suppressor genes, p16(INK4A) and p14(ARF) (p19(ARF) in mice), which regulate cell 
      cycle and cell survival in the retinoblastoma protein (pRb) and p53 pathways, 
      respectively. In mice, the role of p16(INK4A) as the critical tumor suppressor 
      gene at the INK4A locus was challenged when it was found that p19(ARF) only 
      knock-out mice developed tumors, including gliomas. We have analysed the genetic 
      status of the INK4A locus in 105 primary gliomas using both microsatellite 
      mapping (MSM) and quantitative real-time PCR (QRT-PCR). Comparison of the results 
      of the two methods revealed agreement in 67% of the tumors examined. In 
      discordant cases, fluorescence in situ hybridization (FISH) analysis was always 
      found to support QRT-PCR classification. Direct assessment of p14(ARF) exon 
      1beta, p16(INK4A) exon 1alpha and exon 2 by QRT-PCR revealed 43 (41%) homozygous 
      and eight (7%) hemizygous deletions at the INK4A locus. In 49 (47%) gliomas, both 
      alleles were retained. In addition, QRT-PCR, but not MSM, detected hyperploidy in 
      five (5%) tumors. Deletion of p14(ARF) was always associated with co-deletion of 
      p16(INK4A) and increased in frequency upon progression from low to high grade 
      gliomas. Shorter survival was associated with homozygous deletions of INK4A in 
      the subgroup of glioblastoma patients older than 50 years of age (P=0.025, Anova 
      test single factor, alpha=0.05).
FAU - Labuhn, M
AU  - Labuhn M
AD  - Molecular Neuro-Oncology, Department of Research, University Hospital, 
      Schanzenstrasse 46, 4031 Basel, Switzerland.
FAU - Jones, G
AU  - Jones G
FAU - Speel, E J
AU  - Speel EJ
FAU - Maier, D
AU  - Maier D
FAU - Zweifel, C
AU  - Zweifel C
FAU - Gratzl, O
AU  - Gratzl O
FAU - Van Meir, E G
AU  - Van Meir EG
FAU - Hegi, M E
AU  - Hegi ME
FAU - Merlo, A
AU  - Merlo A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA Primers)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Protein p14ARF)
SB  - IM
MH  - Chromosome Mapping
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - DNA Mutational Analysis
MH  - DNA Primers/chemistry
MH  - Gene Deletion
MH  - Gene Expression
MH  - Glioma/*genetics/pathology
MH  - Homozygote
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Polymerase Chain Reaction/*methods
MH  - Proteins/*genetics
MH  - Survival Analysis
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p14ARF
EDAT- 2001/04/21 10:00
MHDA- 2001/05/18 10:01
CRDT- 2001/04/21 10:00
PHST- 2000/09/12 00:00 [received]
PHST- 2000/12/11 00:00 [revised]
PHST- 2000/12/19 00:00 [accepted]
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/05/18 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - 10.1038/sj.onc.1204197 [doi]
PST - ppublish
SO  - Oncogene. 2001 Mar 1;20(9):1103-9. doi: 10.1038/sj.onc.1204197.