Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors.
A principal difference between malignant and normal cells is the aberrant expression of oncogenes. Previously, we have reported on the expression of the insulin-like growth factor 1 receptor (IGF-1-R) in 93% of the human primary breast cancers studied. In the present study, we observed an increased gene copy number of the IGF-1-R in only 19 (2%) of 975 cases studied. The gene copy number of tumors with an amplified IGF-1-R gene varies between 3 and 56 (median, 24 copies). In 11 breast tumor samples with high (greater than or equal to 20 copies) IGF-1-R gene copy numbers, an additional amplification of either the c-myc gene (n = 3) or int-2/bcl-1 genes (n = 5) was observed, whereas no amplification of the HER2/neu gene was detected. The c-fes gene (like the IGF-1-R gene located on chromosome 15q25-qter), was found coamplified with the IGF-1-R in two cases, in one case to the same high extent (38 gene copies, each) and in the other case to only a moderate extent (4 copies of the c-fes gene and 21 copies of the IGF-1-R gene). Tumors with an amplified IGF-1-R gene showed a noticeable increased expression of the IGF-1-R as measured by ligand binding assays on membrane preparations. The median amount of the IGF-1-R protein of the amplified tumors was observed to be 35 times higher when compared to nonamplified tumors (P less than 0.001). Patients with tumors containing a high (greater than or equal to 20 copies) IGF-1-R gene copy number tend to have a shorter median overall survival (42 months; range, 14-120+; n = 8) than patients with tumors having a low amplified (3-10 copies) IGF-1-R gene copy number (median, 77 months; range, 19.5-98+; n = 4).
Berns
E M
EM
Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Klijn
J G
JG
van Staveren
I L
IL
Portengen
H
H
Foekens
J A
JA
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin
D004273:DNA, Neoplasm; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I