PMID- 1584765
OWN - NLM
STAT- MEDLINE
DCOM- 19920616
LR  - 20220309
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 89
IP  - 10
DP  - 1992 May 15
TI  - Amplified and rearranged epidermal growth factor receptor genes in human 
      glioblastomas reveal deletions of sequences encoding portions of the N- and/or 
      C-terminal tails.
PG  - 4309-13
AB  - This study describes genomic rearrangements near the 3' end of the epidermal 
      growth factor receptor (EGFR) gene in eight glioblastomas displaying 
      coamplification and expression of both normal and rearranged EGFR. In four of 
      these cases, it was possible by PCR to amplify tumor EGFR cDNA, which allowed 
      sequence determination of the 3' transcript alterations associated with the 
      rearrangements. Such analysis revealed that the four cases have in common a 
      deletion of 255 bases that encode a portion of the receptor's cytoplasmic domain. 
      The remaining four cases revealed genomic rearrangements in the same region of 
      the gene as those described above and revealed aberrant EGFR transcripts lacking 
      the same 255 bases determined to be missing in the sequenced EGFR cDNAs as well 
      as large regions of contiguous downstream sequences. Therefore, all of the eight 
      cases described here express transcripts that do not encode large C-terminal, 
      intracellular portions of the receptor. In three of the eight cases, the EGFR 
      transcripts displaying a 3' alteration also displayed a 5' inframe deletion of 
      sequences encoding a portion of the extracellular domain, and for one of the 
      corresponding patients it was possible to determine that the two transcript 
      alterations were acquired as separate events. We have now detected the 5' and/or 
      3' alterations in 21 of 32 cases of glioblastoma with EGFR amplification; no 
      genetic alterations have been detected in glioblastomas without EGFR 
      amplification. In combination with previously published reports, these data 
      suggest the in vivo evolution of EGFR toward an increasingly oncogenic potential 
      through gene amplification with subsequent and successive gene alterations.
FAU - Ekstrand, A J
AU  - Ekstrand AJ
AD  - Ludwig Institute for Cancer Research, Karolinska Hospital, Stockholm, Sweden.
FAU - Sugawa, N
AU  - Sugawa N
FAU - James, C D
AU  - James CD
FAU - Collins, V P
AU  - Collins VP
LA  - eng
SI  - GENBANK/X01677
GR  - CA55728/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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA, Neoplasm)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - *Chromosome Deletion
MH  - DNA, Neoplasm/genetics/isolation & purification
MH  - ErbB Receptors/*genetics
MH  - *Gene Rearrangement
MH  - Glioma/*genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction/methods
MH  - RNA, Messenger/*genetics
MH  - RNA, Neoplasm/genetics/isolation & purification
MH  - Transcription, Genetic
PMC - PMC49071
EDAT- 1992/05/15 00:00
MHDA- 1992/05/15 00:01
PMCR- 1992/11/15
CRDT- 1992/05/15 00:00
PHST- 1992/05/15 00:00 [pubmed]
PHST- 1992/05/15 00:01 [medline]
PHST- 1992/05/15 00:00 [entrez]
PHST- 1992/11/15 00:00 [pmc-release]
AID - 10.1073/pnas.89.10.4309 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1992 May 15;89(10):4309-13. doi: 
      10.1073/pnas.89.10.4309.