Cytogenetic studies of 24 renal epithelial tumors with von Hippel-Lindau and fragile histidine triad protein expression correlation.
BACKGROUND
Deletion of the short arm of chromosome 3 (3p deletion) is a cytogenetic abnormality generally associated with clear cell renal cell carcinoma, the most aggressive form of renal epithelial tumor.


OBJECTIVE
To cytogenetically characterize 24 renal tumors in order to check the incidence and the type of 3p deletions, as well as to identify new genes putatively participating in renal tumorigenesis and test the protein products of the von Hippel-Lindau (VHL) and fragile histidine triad (FHIT) genes.


METHODS
We analyzed 24 renal tumors by conventional cytogenetics, comparative genomic hybridization, and fluorescence in situ hybridization. We then performed a comparative expression study of the proteins pVHL and Fhit.


RESULTS
In our series of 24 renal tumors, the 3p deletion was the most frequent genetic alteration (15/24); the other features were partial trisomy 5q, 8p deletion, and monosomy 9 and 14. The 3p deletion was long and terminal, and no interstitial deletion was identified. By immunohistochemistry, we found that for the 2 genes of interest, VHL and FHIT, loss or decrease in protein expression were very frequently observed in clear cell renal cell carcinoma and not always associated with a 3p deletion (14/20 in clear cell renal cell carcinoma).


CONCLUSIONS
Our studies characterize the 3p deletion as long and terminal and identify no interstitial deletion in that chromosome. Fhit and pVHL protein expression loss appear to be independent, as they can be dissociated. Our data are supportive of a role for FHIT (in addition to VHL) in renal tumorigenesis. No other gene with particular potential interest in renal tumorigenesis could be identified among the selected genes.
Gayrard
Nathalie
N
Laboratoire de Génétique Médicale et Chromosomique, Hôpital Arnaud de Villeneuve, Montpellier, France. nathalie.gayrard@montp.inserm.fr
Cacheux
Valère
V
Iborra
François
F
Mourad
Georges
G
Argilés
Angel
A
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C497446:VHL protein, human