Amplification, overexpression, and rearrangement of the erbB-2 protooncogene in primary human stomach carcinomas.
Four of 51 primary gastric carcinomas exhibited amplification of the erbB-2 protooncogene ranging from 2- to 8-fold. In three cases gene amplification affected erbB-2 alleles of normal gene structure as determined by Southern blot analysis. In addition, one tumor displayed gene amplification of an apparently rearranged erbB-2 allele. Analysis of the rearranged allele revealed a structural alteration consistent with an internal deletion of approximately 2 kilobase pairs within the erbB-2 gene. Quantitation of erbB-2 mRNA in these tumors demonstrated that gene amplification coincided with overexpression of erbB-2 mRNA ranging from 8- to 32-fold above levels observed in stomach tumors without gene amplification. Furthermore, in one of the tumors with amplified normal size erbB-2 restriction fragments, elevated erbB-2 mRNA levels consisted of the normal size 5-kilobase transcript. Thus, overexpression of normal size erbB-2 mRNA accompanies gene amplification in primary stomach tumors. In addition, evidence for erbB-2 gene rearrangement suggests a role for such alteration in the development of certain gastric carcinomas.
Park
J B
JB
Department of Biochemistry, College of Medicine, Seoul National University, Korea.
Rhim
J S
JS
Park
S C
SC
Kimm
S W
SW
Kraus
M H
MH
D015152:Blotting, Northern; D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics*; D015342:DNA Probes; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D013274:Stomach Neoplasms / Q000235:genetics*
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases