12th Ljudevit Jurak
International Symposium on
June 1-2, 2001
|GENETIC INSTABILITIES OF THE E-CADHERIN GENE (CHH1)
IN RENAL CELL CARCINOMA
K. Gall-Trošelj*, K. Radiæ**, K. Paveliæ*,
Department of Biology, School of Medicine, University of Zagreb, Croatia
*Division of Molecular Medicine, Ruðer Boškoviæ Institute,
**School of Medicine, University of Zagreb, Zagreb, Croatia
|E-cadherin is one of the most important molecules of cell-cell adhesion
in epithelial tissues, generally localized on the surfaces of epithelial
cells in a region of cell-cell contact that is known as the adherens junction.
In our study the role of the tumor suppressor gene E-cadherin (CDH1) was
investigated in renal cell carcinoma (RCC). Our previous study showed that
the APC tumor suppressor gene is involved in renal carcinogenesis, demonstrating
indirectly that cell-cell interaction is one of the targets involved in
renal cell carcinoma progression. Since E-cadherin is bound to the APC
gene via beta-catenin, we were interested to see any detection of E-cadherins
involvement in RCC.
Forty-five human renal cell carcinomas together with autologous peripheral
blood samples were tested for gene instability. Using specific oligonucleotide
primers E-cadherin gene was analyzed by PCR amplification of the tetranucleotide
repeat polymorphic marker (D16S752) and the alleles were visualized by
The polymorphic marker for E-cadherin gene was highly informative (39/43,
91%). Our results demonstrate that from 39 informative tumor samples 2
(5%) demonstrated LOH.
Interestingly, in another three RCC samples we detected another type
of genomic instability; replication error (RER+). Both samples which showed
LOH of the E-cadherin had also LOH of the APC gene, while only one RER+
sample of the E-cadherin gene showed LOH at the APC locus. The overall
number of genetic instabilities in our sample was 5/39 (13%).
Pathohistological diagnosis showed no correlation with molecular data.
Our results suggest that alterations in E-cadherin gene are involved in
the evolution and progression of RCC. Microsatellite genetic instability
of the E-cadherin gene indicates that another cellular mechanism, mismatch
repair, is targeted in RCC.