Abstract：
OBJECTIVE:To investigate the incidence of loss of heterozygosity (LOH) and microsatellite instability (MI) in human renal cell carcinoma (RCC), and to determine a possible activation of H-ras oncogene in these tumours via implication of its polymorphic regions within the first intron and 3' ends. METHODS:In the present study, we investigated the incidence of MI and LOH in 22 RCCs, using a bank of 8 microsatellite markers located on chromosomes 2 (IL1A), 3 (D3S1234), 8 (MYC), 14 (D14S51) and 17 (THRA1, D17S250, D17S579). We also studied the microsatellite DNA of the H-ras oncogene within the first intron (HRM) and the minisatellite DNA of the variable tandem repeat (VTR), which is located 1,000 bp downstream of the H-ras gene and possesses enhancer activity, for genetic instability. Alterations of the 28-bp repetition core were studied employing restriction fragment length polymorphism analysis. RESULTS:MI and LOH were observed in 8 (4 MI and 4 LOH) out of 22 (18%) specimens at 3p21.1-p14.2 and 17q21, indicating the presence of putative tumour suppressor genes (TSGs) at these loci. Alterations of the 28-bp repetition core of H-ras VTR were found in 2 out of 22 cases (9%), while point mutations of the same repetition core were detected in only 1 case (5%). Additionally, 1 case (5%), showed LOH. CONCLUSIONS:Our results indicate that genetic instability is a detectable phenomenon in human RCC and it might be associated with the development of the disease. LOH at 3p21.1-p14.2 and 17q21 suggests that important TSGs may be located on these chromosomal regions involved in the tumorigenesis or progression of RCC. Considering the fact that the DNA sequence of this VTR region contains a target area for transcription and other regulation factors of H-ras gene expression, these findings could be of importance as regards the involvement of this gene in the process of carcinogenesis in RCC.
journal_name
Eur Uroljournal_title
European urologyauthors
Diakoumis E,Sourvinos G,Kiaris H,Delakas D,Cranidis A,Spandidos DAdoi
10.1159/000019541subject
Has Abstractpub_date
1998-01-01 00:00:00pages
227-32issue
2eissn
0302-2838issn
1873-7560pii
eur33227journal_volume
33pub_type
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