Comparative evaluation of microsatellite marker, AP-PCR and CGH studies in primary renal cell carcinoma.
Renal cancer consists of a heterogeneous tumor group which is characterized by complex cytogenetic and molecular genetic abnormalities. In this study, three different techniques were applied to screen renal cancers for genetic alterations. We studied 99 primary, sporadic renal cancers (96 renal cell carcinomas and three other renal cancers) by a comparative evaluation of different microsatellite markers, comparative genomic hybridization (CGH) and AP-PCR. The AP-PCR produces a genomic fingerprint after an AluEI DNA restriction digest of tumor DNA samples. Microsatellite alterations were investigated using nine microsatellite markers spanning well-known regions of FhiT and VHL (3p14.2, 3p26) but also of oncogenes and tumor suppressor genes like Myc-L1 and TP53Alu (1p32, 17p13.1). To receive a genomic fingerprint, AP-PCR was carried out for all patient samples. Performing AP-PCR, only one case out of 99 displayed genomic imbalance. Seven of 99 investigated primary renal cancers showed alterations in up to four microsatellite loci (TP53Alu, Myc-L1, D3S1300, D3S1560, D3S1317, D3S4260). Three markers (Bat25, Bat26, REN) did not reveal any aberrations within the tested tumor samples. Six cases with microsatellite alterations and four without were examined by CGH. Five samples yielded aberrations, four of them were positive for microsatellite alterations. Only one tumor sample displayed microsatellite alterations, shift patterns in AP-PCR and alterations analyzed by CGH. Our data suggest that genomic aberrations found by microsatellite analysis are also detectable by CGH with the restriction of a minimum of alterated DNA of >10 Mb. Based on this study of RCC and in contrast to other reports for solid tumors, we conclude that AP-PCR is far less informative in investigation of renal cancers.
Hoefling
Christian
C
Department of Urology, Technical University Dresden, D-01307 Dresden, Germany.
Schmidt
Hannelore
H
Meinhardt
Matthias
M
Lohse
Andrea
A
Taubert
Helge
H
Fuessel
Susanne
S
Schmidt
Uta
U
Schuster
Katja
K
Baretton
Gustavo
G
Wirth
Manfred P
MP
Meye
Axel
A
D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007680:Kidney Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction
D005819:Genetic Markers