TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe

K. Szymańska, L. E. Moore, N. Rothman, W. H. Chow, F. Waldman, E. Jaeger, T. Waterboer, L. Foretova, M. Navratilova, V. Janout, H. Kollarova, D. Zaridze, V. Matveev, D. Mates, N. Szeszenia-Dabrowska, I. Holcatova, V. Bencko, F. Le Calvez-Kelm, S. Villar, M. PawlitaP. Boffetta, P. Hainaut, P. Brennan

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)92-98
Number of pages7
JournalCancer Letters
Volume293
Issue number1
DOIs
StatePublished - Jul 1 2010

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Keywords

  • Cancer
  • EGFR
  • Renal carcinoma
  • TP53 mutations
  • VHL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Szymańska, K., Moore, L. E., Rothman, N., Chow, W. H., Waldman, F., Jaeger, E., Waterboer, T., Foretova, L., Navratilova, M., Janout, V., Kollarova, H., Zaridze, D., Matveev, V., Mates, D., Szeszenia-Dabrowska, N., Holcatova, I., Bencko, V., Le Calvez-Kelm, F., Villar, S., ... Brennan, P. (2010). TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe. Cancer Letters, 293(1), 92-98. https://doi.org/10.1016/j.canlet.2009.11.024