Tandem duplication of the epidermal growth factor receptor tyrosine kinase and calcium internalization domains in A-172 glioma cells.
Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene occur frequently in malignant gliomas. Rearrangement may also lead to the expression of potentially oncogenic EGFR deletion mutants. Data presented here indicate the existence of a 190 kDa mutant form of the EGFR in A-172 glioma cells that is substantially different from the deletion mutants characterized previously. The EGFR-like protein is expressed along with the 170 kDa wild type EGFR. It is detectable with antibodies to both extracellular and intracellular regions of the EGFR, but is not crossreactive with other HER-family members. The wild type and mutant receptors undergo phosphorylation in response to treatment with TGFalpha and are associated with expression of both 10.5 kb and 11.5 kb EGFR-related transcripts. Combined reverse transcription-polymerase chain reaction (RT-PCR) identifies a unique transcript in A-172 cells that encodes an in-frame, tandem duplication of both tyrosine kinase and calcium internalization (TK/CAIN) domains (exons 18 through 26). The duplication of these domains is associated with a specific genomic rearrangement between potential v-myb and c-myb consensus binding sites within introns 26 and 17 of the EGFR gene resulting in the formation of a chimeric intron.
Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
R A
RA
Fenstermaker
M J
MJ
Ciesielski
G J
GJ
Castiglia
D000951:Antigens, Neoplasm / Q000235:genetics; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D015321:Gene Rearrangement; D005910:Glioma / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007438:Introns; D005810:Multigene Family; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA
D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D066246:ErbB Receptors