Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system

Abstract

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 at 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 spotswhere brain tumour tissues show a predilection for point mutation.