Genetic instability of 3p12-p21-specific microsatellite sequences in renal cell carcinoma.
OBJECTIVE
To determine the role of structural alterations of human chromosome region 3p12-p21 in the possible inactivation of one or more tumour-suppressor genes in the pathogenesis of renal cell carcinoma (RCC), lung cancer and other neoplasms.


METHODS
As microsatellite instability (MI), in particular MI with loss of heterozygosity (LOH), may indicate putative tumour-suppressor gene loci, 20 kidney tumours, including 14 clear cell carcinomas and six non-clear cell neoplasms, were investigated with 10 polymorphic simple sequence-repeat markers spanning 3p12-p21. Six of these markers map to the region of deletion flanked by markers D3S1285 and D3S1295 bracketing the t(3;8) translocation break-point in 3p14.2 of hereditary RCC.


RESULTS
Twelve of 14 clear cell RCCs displayed MI for at least one locus, as opposed to none of the non-clear cell tumours (P = 0.001). Locus D3S1274 in 3p13 located in the region deleted in lung cancer line U2020 and loci D3S1313 and D3S1300 in 3p14.3 characterized common regions of instability and LOH. Two patients with RCC who also had lung cancer and colon cancer, respectively, showed LOH at D3S1313 or D3S1300 as the only alterations of their kidney tumours.


CONCLUSIONS
These results suggest that human chromosome region 3p14.3 distal to the hereditary t(3;8) translocation breakpoint and the region deleted in the U2020 lung cancer cell line might be involved in the tumorigenesis or progression of clear cell RCC.
Willers
C P
CP
Department of Medical Oncology, University of Essen Medical School, Germany.
Siebert
R
R
Bardenheuer
W
W
Lux
A
A
Michaelis
S
S
Seeber
S
S
Luboldt
H J
HJ
Opalka
B
B
Schütte
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged
D005819:Genetic Markers