Germline mutation of the folliculin gene (BHD) at chromosome 17p11.2 is associated with the development of multiplex hamartomas of the hair follicles, chromophobe renal cell carcinomas (RCC) and renal oncocytomas (RO). We have analyzed the folliculin gene with sequencing for mutations and the chromosome 17p11.2 with microsatellites for allelic changes in sporadic ROs and chromophobe RCCs. Allelic loss at chromosome 17 was seen in 8 of 8 chromophobe RCCs whereas none of the 8 RO showed alteration at this chromosomal region. Sequencing all exons from genomic DNA failed to disclose mutations of the folliculin gene in any of the tumors. We found a single nucleotide polymorphism (SNP) of G/A (nt 74) at the first exon in the untranslated region of the folliculin gene. We did not find a correlation between the SNP G/A or loss of the G allele and the expression level of either splice variants of the folliculin gene. Our data suggest the folliculin gene does not play a role in the tumorigenesis of sporadic chromophobe RCCs and renal oncocytomas. Key words: renal cell cancer; folliculin gene; mutation; allelic changesThe Birt-Hogg-Dubé (BHD) syndrome, an autosomal dominant disease, is associated with the development of multiplex hamartomas of the hair follicles, renal cell tumors and spontaneous pneumothorax. 1-3 Linkage analysis of several families located the gene to chromosome 17p11.2 region. 4,5 Germline mutation of the folliculin gene (in most cases a C insertion or deletion in the hypermutable (C) 8 tract at nt 1733-1740 in exon 11) has been found recently in affected family members. 6,7 A systematic histopathological survey indicated that most patients with BHD syndrome develop a particular type of renal cell tumor, the overwhelming majority of which corresponds to chromophobe RCCs (34%) or so called "hybrid" neoplasms (50%) resembling a mixture of chromophobe RCC and RO. 8 Previous CGH and microsatellite studies indicated that chromosome 17 is lost in ϳ80% of sporadic chromophobe RCC. 9,10 To establish the possible involvement of the folliculin gene in the tumorigenesis we have searched for mutation by sequencing the exons 1-14 in sporadic chromophobe RCC and ROs. Although microsatellite allelotyping confirmed a frequent LOH at chromosome 17p11.2 region in chromophobe RCCs, our study failed to detect mutation of the folliculin gene in the special types of sporadic tumors resembling those associated with the BHD syndrome. MATERIAL AND METHODS Tumor samples, DNA and RNA extractionFresh tumor and normal kidney parenchymal tissues were obtained by nephrectomy at the Departments of Urology, Hannover Medical School and the Heidelberg University, Germany between 1986 -8 and 1993-7, respectively. A section of tumor was immediately snap-frozen in liquid nitrogen and stored at Ϫ80°C and the remaining tissue was fixed in 4% buffered formaldehyde for histological report. The diagnosis was established according to the Heidelberg Classification of Renal Cell Tumors. 11 For DNA extraction frozen tumor sample was placed in a pla...
Background: Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type.
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