PMID- 12543796
OWN - NLM
STAT- MEDLINE
DCOM- 20030313
LR  - 20220317
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 2
DP  - 2003 Jan 15
TI  - Selection pressures of TP53 mutation and microenvironmental location influence 
      epidermal growth factor receptor gene amplification in human glioblastomas.
PG  - 413-6
AB  - Epidermal growth factor receptor (EGFR) gene amplification occurs in 
      glioblastomas as so-called double minutes. Because double minutes are 
      extrachromosomal fragments, selection pressures must operate to maintain high 
      EGFR copy number over multiple cell divisions. In analyses of glioblastoma 
      lysates, EGFR amplification has been observed almost exclusively in glioblastomas 
      harboring wild-type TP53 genes, which raises the alternative hypotheses that TP53 
      mutation either prevents amplification or selects against maintenance of 
      EGFR-amplified cells. To address these possibilities at the cellular level, we 
      studied 14 glioblastomas for TP53 mutation and EGFR gene amplification status, 
      using fluorescence in situ hybridization (FISH) for the latter. Remarkably, four 
      of the six cases with TP53 mutation had isolated EGFR-amplified cells in 
      different regions, demonstrating that EGFR amplification occurs frequently at the 
      cellular level in TP53-mutant glioblastomas. Thus, TP53 mutation does not prevent 
      EGFR amplification but does not facilitate selection of EGFR-amplified cells. Of 
      the eight cases without TP53 mutation, five had widespread EGFR amplification. In 
      four of these five cases, multiple regions of the tumor were available for 
      examination; FISH demonstrated a gradation of EGFR amplification, with highly 
      amplified cells, primarily at the invading edges rather than the relatively solid 
      tumor centers, suggesting that EGFR overexpression, when selected for in vivo, 
      may be related to tumor invasion.
FAU - Okada, Yoshifumi
AU  - Okada Y
AD  - The Molecular Neuro-Oncology Laboratory and Molecular Pathology Laboratory, 
      Department of Pathology and Neurosurgical Service, Massachusetts General Hospital 
      and Harvard Medical School, 149 13 St., Charlestown, Massachusetts 02129, USA.
FAU - Hurwitz, Edward E
AU  - Hurwitz EE
FAU - Esposito, John M
AU  - Esposito JM
FAU - Brower, Melissa A
AU  - Brower MA
FAU - Nutt, Catherine L
AU  - Nutt CL
FAU - Louis, David N
AU  - Louis DN
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - ErbB Receptors/*genetics
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Genes, p53/*genetics
MH  - Glioblastoma/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Mutation
MH  - Paraffin Embedding
EDAT- 2003/01/25 04:00
MHDA- 2003/03/14 04:00
CRDT- 2003/01/25 04:00
PHST- 2003/01/25 04:00 [pubmed]
PHST- 2003/03/14 04:00 [medline]
PHST- 2003/01/25 04:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Jan 15;63(2):413-6.