PMID- 10665922
OWN - NLM
STAT- MEDLINE
DCOM- 20000217
LR  - 20190722
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 31
IP  - 1
DP  - 2000 Jan
TI  - Incidence of p14ARF gene deletion in high-grade adult and pediatric astrocytomas.
PG  - 115-9
AB  - The INK4a-ARF locus encodes 2 separate proteins through differential splicing of 
      alternative first exons to produce p16INK4a (exon 1alpha) and p14ARF (exon 1beta) 
      products in human cells. The p16INK4a protein inhibits the cyclin D-dependent 
      kinases (CDK) that control the phosphorylation of the Rb protein and cell 
      proliferation. The p14ARF gene product can complex with and sequester the MDM2 
      protein within the nucleus, thus modulating the activity of the p53 protein. Loss 
      of p16INK4a expression would disrupt the retinoblastoma (Rb)/p16INK4a/cyclin 
      D-dependent kinase (CDK4) pathway, whereas loss of p14ARF expression would 
      inactivate both the Rb and p53/ MDM2/p14ARF pathways through MDM2, which can 
      complex with either Rb or p53. Loss of the p16INK4a gene on 9p21 has been 
      documented in a wide range of human tumors, including one third of glioblastomas. 
      However, in tumors showing homozygous loss of exon 2 of the p16INK4a gene, loss 
      of exon 1beta of the p14ARF gene has not been established. In this study, we have 
      assessed deletion of the p14ARF gene in 29 pediatric and 107 adult high-grade 
      astrocytomas and 9 glioma cell lines, using multiplex PCR analysis for exon 
      1beta. We found homozygous deletions for exon 1alpha and exon 1beta in 3 of 29 
      (10%) of the pediatric cases (2 grade III, 1 grade IV), 25 of 107 (23%) of the 
      adult cases (6 grade III and 19 grade IV), and 8 of 9 (89%) of the glioma cell 
      lines. Therefore, loss of the INK4a-ARF locus in high-grade astrocytomas may 
      contribute to the highly malignant behavior and treatment resistance of these 
      tumors through elimination of multiple checkpoint cell cycle control proteins.
FAU - Newcomb, E W
AU  - Newcomb EW
AD  - Department of Pathology, Kaplan Comprehensive Cancer Center, New York University 
      Medical Center, NY 10016, USA.
FAU - Alonso, M
AU  - Alonso M
FAU - Sung, T
AU  - Sung T
FAU - Miller, D C
AU  - Miller DC
LA  - eng
GR  - CA 16087/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Protein p14ARF)
SB  - IM
MH  - Adult
MH  - Astrocytoma/*genetics/*pathology
MH  - Carrier Proteins/genetics/metabolism
MH  - Child, Preschool
MH  - Cyclin-Dependent Kinase Inhibitor p16
MH  - *Gene Deletion
MH  - Glioblastoma/genetics
MH  - Glioma/genetics
MH  - Homozygote
MH  - Humans
MH  - Immunohistochemistry
MH  - Proteins/*genetics
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p14ARF
EDAT- 2000/02/09 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/02/09 09:00
PHST- 2000/02/09 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/02/09 09:00 [entrez]
AID - S0046-8177(00)80207-5 [pii]
AID - 10.1016/s0046-8177(00)80207-5 [doi]
PST - ppublish
SO  - Hum Pathol. 2000 Jan;31(1):115-9. doi: 10.1016/s0046-8177(00)80207-5.