Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system.
Point mutations in the transmembrane domain of c-erbB-2 gene in human brain tumours were studied by DNA amplification with the polymerase chain reaction method. Amplified gene fragments in M13 phage vector were cloned, and subsequent nucleotide sequences were determined. Studied specimens were 10 human malignant and 3 human benign tumours of the central nervous system, and a normal human placenta. In malignant tissues, Val-to-Glu mutation that induces transforming activity of c-erbB-2 did not appear to codon 659 of c-erbB-2. In malignant tissues, many other types of mutations appeared in low frequency, either at codon 659 or other positions of the transmembrane domain of c-erbB-2. The ratio of mutated genes to normal genes was very low in all specimens of malignant tumours. The point mutations were not observed in benign brain tumour or normal human placental tissues. The transmembrane domain of c-erbB-2 may have several highly mutable hot spots, where brain tumour tissues show a predilection for point mutation.
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
H
H
Kamitani
M
M
Mariyama
T
T
Hori
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S
Nishimura
D000595:Amino Acid Sequence; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D003062:Codon / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases
D003062:Codon; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases