Document Detail


VHL and FHIT locus loss of heterozygosity is common in all renal cancer morphotypes but differs in pattern and prognostic significance.
MedLine Citation:
PMID:  11406557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deletions involving 3p are believed to be typical for conventional (clear cell) renal cell carcinoma (cRCC), with confirmed and suspected targets being the VHL and FHIT tumor suppressor genes, respectively. By contrast, 3p deletions are felt to be rare in papillary RCC (pRCC) and chromophobe RCC (chRCC); however, this belief is based on relatively scant data. In particular, 3p14.2 deletions, possibly resulting in FHIT inactivation, have been rarely studied in pRCC or chRCC even though they may be relevant in early renal tumorigenesis. We therefore examined 3p deletion rates and patterns in pRCC and chRCC with particular attention to 3p14.2. We examined 16 chRCCs and 27 pRCCs for loss of heterozygosity (LOH) at 3p25-26 and 3p14.2 using 13 well-mapped microsatellite markers. Those pRCC with LOH at 3p25-26 were also screened for VHL gene mutations. The results were correlated with tumor histology and patient outcome and compared with data we had obtained previously on cRCC. We found similar overall 3p LOH rates in pRCC (59%), chRCC (86.6%), and cRCC (75.8%). In pRCC and chRCC, LOH at 3p25-26 was more common than at 3p14.2, whereas the converse was true for cRCC. In the pRCC with 3p25-26 LOH, we confirmed that this was not associated with mutations of the VHL gene. At 3p14.2, LOH rates of pRCC were lower than those of cRCC and chRCC (p<0.02). All morphotypes showed a predominately interstitial LOH pattern, which was most pronounced in the 3p14.2 region in cRCC. 3p LOH in chRCC was associated with improved patient outcome, mirroring our previous cRCC data. We conclude that 3p LOH is a universal phenomenon in RCC, but has different underlying mechanisms, molecular targets, and implications in the different morphotypes, although FHIT inactivation may play a role in both cRCC and chRCC tumorigenesis.
Authors:
M Velickovic; B Delahunt; S Störkel; S K Grebem
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  61     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-14     Completed Date:  2001-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4815-9     Citation Subset:  IM    
Affiliation:
Department of Pathology and Molecular Medicine, Wellington School of Medicine, Wellington, New Zealand.
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MeSH Terms
Descriptor/Qualifier:
Acid Anhydride Hydrolases*
Adenocarcinoma, Clear Cell / genetics,  pathology
Carcinoma, Papillary / genetics,  pathology
Carcinoma, Renal Cell / genetics*,  pathology
Chromosomes, Human, Pair 3 / genetics
Female
Humans
Kidney Neoplasms / genetics*,  pathology
Ligases*
Loss of Heterozygosity*
Male
Middle Aged
Neoplasm Proteins*
Prognosis
Proteins / genetics*
Tumor Suppressor Proteins*
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/Proteins; 0/Tumor Suppressor Proteins; 0/fragile histidine triad protein; EC 3.6.-/Acid Anhydride Hydrolases; EC 6.-/Ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein

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