Genetic changes of the E-cadherin and APC tumour suppressor genes in clear cell renal cell carcinoma.
OBJECTIVE
The roles of tumour suppressor genes: adenomatous polyposis coli (APC) and E-cadherin (CDH1) were investigated in clear cell renal cell carcinoma.


METHODS
Forty-five human clear cell renal cell carcinomas were tested for APC gene instability by polymerase chain reaction/loss of heterozygosity using the restriction fragment length polymorphism method. E-cadherin gene was analysed by PCR amplification of tetranucleotide marker (D16S752) and the alleles were visualised by PAGE/silver staining.


RESULTS
The overall proportion of loss of heterozygosity of the APC gene was 37.5% (9/24). D16S752 marker linked to E-cadherin gene (informativeness 91%) revealed three samples with loss of heterozygosity (7.5%). Interestingly, replication error phenotype was detected in 9.1% of clear cell renal cell carcinoma samples. Multivariate statistical analysis of samples informative for both APC and E-cadherin genes showed that, in this data set, loss of heterozygosity of the APC gene is correlated with advanced age and more severe TNM stages. Genetic changes of the E-cadherin gene, on the other hand, appear to be correlated with younger age groups and less severe TNM stages.


CONCLUSIONS
Our results suggest that alterations, both in APC and E-cadherin genes, are involved in the evolution and progression of clear cell renal cell carcinoma. Microsatellite genetic instability of the E-cadherin gene indicates that another cellular mechanism, mismatch repair, may also be targeted in this malignancy.
Pećina-SLaus
Nives
N
Department of Biology, School of Medicine University of Zagreb, Zagreb, Croatia. nina@mef.hr
Gall-TroSelj
Koraljka
K
SLaus
Mario
M
Radić
KreSimir
K
NikuSeva-Martić
Tamara
T
Pavelić
KreSimir
K
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D017491:Genes, APC; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D015820:Cadherins; D004273:DNA, Neoplasm