Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor alpha receptor expression in human malignant gliomas.
The aim of this study was to examine platelet-derived growth factor alpha receptor (PDGFR-alpha) expression in gliomas of various degrees of malignancy and to correlate the findings with genetic alterations present in the same tumor samples. We analyzed 83 tumors by in situ hybridization using a PDGFR-alpha cRNA probe. Increased PDGFR-alpha mRNA expression was observed in astrocytic tumors of all stages of malignancy, although the highest levels were found in glioblastoma multiforme. To evaluate the frequency of PDGFR-alpha gene amplification, differential PCR requiring less DNA than Southern analysis was used with fluorescence-labeled primers corresponding to the kinase insert region of the PDGFR-alpha. Only 7 of 43 glioblastomas and none of the other tumors tested showed amplification of the PDGFR-alpha gene, suggesting that a mechanism other than gene amplification is responsible for the overexpression of PDGFR-alpha in glial brain tumors. Comparison of the in situ hybridization data with genetic alterations in the same tumor material showed a significant correlation of loss of heterozygosity on chromosome 17p (Fisher's exact, P < 0.0002) with high expression levels of PDGFR-alpha. Because that was the case in both low- and high-grade astrocytomas, our data imply that PDGFR-alpha is actively involved in tumor cell proliferation in early and late stages of glioma development. The association of PDGFR-alpha expression with a distinct subset of glioblastomas characterized by loss of heterozygosity 17p further supports the differentiation of these tumors into molecular variants.
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
M
M
Hermanson
K
K
Funa
J
J
Koopmann
D
D
Maintz
A
A
Waha
B
B
Westermark
C H
CH
Heldin
O D
OD
Wiestler
D N
DN
Louis
A
A
von Deimling
M
M
Nistér
D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018075:RNA, Complementary / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics
D018075:RNA, Complementary; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor