Molecular analysis of genetic changes in the origin and development of renal cell carcinoma.
Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 which suggests the presence of a tumor suppressor gene at this location. In order to more precisely define the location of the renal cell carcinoma gene and to differentiate molecular changes occurring in early stages of renal neoplasia versus those occurring later in malignant progression, DNA from normal and tumor tissue from 60 patients with various stages of renal cell carcinoma was analyzed for loss of alleles at different chromosomal loci. In tumor tissue from 51 of 58 evaluable patients (88%) there was loss of heterozygosity at one or more of 10 loci tested on chromosome 3 independently of tumor stage. Analysis of the genotypes identified the distal portion of 3p bounded by D3S2 and D3S22 (3p21-26) as the region of the disease gene. In tumor tissue from patients with advanced renal cell carcinoma, we found loss of heterozygosity on chromosome 11p in 5 of 21 (24%), on chromosome 13 in 3 of 9 (33%), and on chromosome 17 in 2 of 19 (11%). We found no loss of heterozygosity at the loci on chromosomes 11, 13, or 17 in tumor tissue from patients with localized renal cell carcinoma (N = 5). These data suggest the existence of a tumor suppressor gene on chromosome 3p which may be essential to the genesis of sporadic renal cell carcinoma and that other tumor suppressor genes are associated with progression of this malignancy.
Anglard
P
P
Urologic Oncology Section, National Cancer Institute, Bethesda, Maryland 20892.
Tory
K
K
Brauch
H
H
Weiss
G H
GH
Latif
F
F
Merino
M J
MJ
Lerman
M I
MI
Zbar
B
B
Linehan
W M
WM
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000302:isolation & purification; D015342:DNA Probes; D003720:Densitometry; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D004247:DNA