TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.
Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas.
International Agency for Research on Cancer (IARC), Lyon, France.
K
K
Szymańska
L E
LE
Moore
N
N
Rothman
W H
WH
Chow
F
F
Waldman
E
E
Jaeger
T
T
Waterboer
L
L
Foretova
M
M
Navratilova
V
V
Janout
H
H
Kollarova
D
D
Zaridze
V
V
Matveev
D
D
Mates
N
N
Szeszenia-Dabrowska
I
I
Holcatova
V
V
Bencko
F
F
Le Calvez-Kelm
S
S
Villar
M
M
Pawlita
P
P
Boffetta
P
P
Hainaut
P
P
Brennan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D020868:Gene Silencing; D018773:Genes, erbB-1; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D014407:Tumor Cells, Cultured