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Cytogenetic investigation of synchronous bilateral renal tumors
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A MAJOR ROLE FOR A 3P21 REGION AND LACK OF INVOLVEMENT OF THE t(3;8) BREAKPOINT REGION IN THE DEVELOPMENT OF RENAL CELL CARCINOMA SUGGESTED BY LOSS OF HETEROZYGOSITY ANALYSIS
Abstracts
COMPARATIVE GENOMIC HYBRIDIZATION ANALYSIS OF WlLMS TUMORS M. Steenman, M. de Meulemeester, C. Wiesmeijer, E. Redeker, A. Westerveld, P. Vo0te, R. Slater, M. Mannens Instltuut voor Antropogenetlca, Unlversltelt van Amsterdam, Academlsch Medisch Centrum, The Netherlands.
PMJF. Veldhuis ~,A. van den Berg ~, MMF. Hulsbeek~, D. de Jong ~, K. Kok ~,J. RocheL CHCM. Buys~ Dept. of Medical Genetics, University of Groningen, The Netherlands. 2Div. of Medical Oncology, University of Colorado Health Sciences Center, Denver CO 80262, USA
In a loss of heterozygosity analysis of 3p we examined 44 sporadic cases of renal cell carcinoma (RCC) and matched normal tissue with 27 microsatellite markers. The majority of these markers clustered in three regions that have been suggested to be involved in the development of RCC, namely the p25 region, where the Von Hippel Lindau (VHL) gene is located; the p21 region, which has been identified as the common region of overlap of heterozygous deletions; and the pl 4 region, which is the location of the constitutional t(3;8) breakpoint occurring in an RCC family. Our analysis shows that when deletions were detected the 3p21 region was always included. The t(3;8) breakpoint region showed the lowest percentage of loss of heterozygosity. Moreover, in three cases the t(3;8) breakpoint region retained heterozygosity, whereas a region more proximal to the breakpoint showed allelic losses. This supports exclusion of the t(3;8) region from a role in the development of sporadic RCC. In a number of tumours two or three 3p deletions were present separated by a region of retention of heterozygosity. In these tumours deletions at 3p21 occurred in combination with deletions of either the VHL region, or the region proximal to the t(3;8), or both, suggestive of multiple gene involvement in the development of sporadic RCC with a primary role of the 3p21 region.
CYTOGENETIC INVESTIGATION OF SYNCHRONOUS BILATERALRENAL TUMORS P. Dal Cin ~, H. Van PoppelL B. Van Damme 3, L. BaertL H. Van den Berghe ~ ~Centrum voor Menselijke Erfelijkheid, 2Department Urologie en 3Departement Pathologische Ontleedkunde, Katholieke Universiteit Leuven, Belgium
Cytogenetic investigations on synchronous bilateral renal tumors are scarce. We here report our findings on 13 renal tumors from 5 patients and review the literature. In bilateral as well as in solitary tumors, cytogenetic findings in each tumor correlated with the histological patterns i.e. combinations of trisomies for papillary renal cell carcinoma, loss of 3p-material for nonpapillary renal cell carcinoma, coincident loss of the Y chromosome and chromosome 1 in oncocytomas. Bilateral multifocal RCCs were always of the papillary type and the the karyotypes showed more or less the same numerical anomalies, with trisomies in different combinations in tumors within the same kidney as well as in both kidneys. Structural changes, in contrast, were different from tumor to tumor
Although the genetical changes occurring in Wilms tumor (an embryonal tumor of the kidney) have been investigated with cytogenetic and molecular techniques, there have been no reports up until now on comparative genomic hybridization (CGH) studies. In this study we applied a modified CGH protocol to analyze a series of ~47 Wilms tumors: labeled test and control DNA, Cot-I DNA and normal chromosomes were denatured simultaneously under a coverslip using a microwave. In our experience this method of denaturation has improved the intensity of the fluorescent signals and the morphology of the chromosomes. An additional advantage is that the quality of the CGH is no longer dependent on the batch of lymphocytes used to obtain the chromosome spreads. The majority of the tumors analyzed in this study had already been characterized by Southern analysis with markers from chromosomes i, 3p, 5q, 1 lp, 13q, 16q, 17p and 22q. These Southern data confirmed our CGH results. CGH analysis showed losses of lp, 4q, 7p, lip, 16q and 17p and gains of 1q, 7q, 8, 12q, 17q and 18. With the exception of loss of 4q all these chromosomal changes have been reported previously in studies using techniques other than CGH. However, the percentage of tumors showing loss of 11 p by CGH was strikingly lower than the percentage of tumors showing LOH of 1 Ip by Southern analysis. This can be explained by the fact that many Wilms tumors show uniparental disomy of I I p (as demonstrated with LOH studies in our series of tumors). ~63% of the tested tumors did not show any chromosomal losses or gains. Currently we are in the process of confirming losses found by CGH using microsatellite markers. Since our improved protocol has been proved to be a reliable routine technique for CGH analysis, we are using this technique to screen hepatoblastomas and rhabdomyosarcomas.
A MAJOR ROLE FOR A 3P21 REGION AND LACK OF INVOLVEMENT OF THE t(3;8) BREAKPOINT REGION IN THE DEVELOPMENT OF RENAL CELL CARCINOMA SUGGESTED BY LOSS OF HETEROZYGOSITY ANALYSIS
Abstracts
COMPARATIVE GENOMIC HYBRIDIZATION ANALYSIS OF WlLMS TUMORS M. Steenman, M. de Meulemeester, C. Wiesmeijer, E. Redeker, A. Westerveld, P. Vo0te, R. Slater, M. Mannens Instltuut voor Antropogenetlca, Unlversltelt van Amsterdam, Academlsch Medisch Centrum, The Netherlands.
PMJF. Veldhuis ~,A. van den Berg ~, MMF. Hulsbeek~, D. de Jong ~, K. Kok ~,J. RocheL CHCM. Buys~ Dept. of Medical Genetics, University of Groningen, The Netherlands. 2Div. of Medical Oncology, University of Colorado Health Sciences Center, Denver CO 80262, USA
In a loss of heterozygosity analysis of 3p we examined 44 sporadic cases of renal cell carcinoma (RCC) and matched normal tissue with 27 microsatellite markers. The majority of these markers clustered in three regions that have been suggested to be involved in the development of RCC, namely the p25 region, where the Von Hippel Lindau (VHL) gene is located; the p21 region, which has been identified as the common region of overlap of heterozygous deletions; and the pl 4 region, which is the location of the constitutional t(3;8) breakpoint occurring in an RCC family. Our analysis shows that when deletions were detected the 3p21 region was always included. The t(3;8) breakpoint region showed the lowest percentage of loss of heterozygosity. Moreover, in three cases the t(3;8) breakpoint region retained heterozygosity, whereas a region more proximal to the breakpoint showed allelic losses. This supports exclusion of the t(3;8) region from a role in the development of sporadic RCC. In a number of tumours two or three 3p deletions were present separated by a region of retention of heterozygosity. In these tumours deletions at 3p21 occurred in combination with deletions of either the VHL region, or the region proximal to the t(3;8), or both, suggestive of multiple gene involvement in the development of sporadic RCC with a primary role of the 3p21 region.
CYTOGENETIC INVESTIGATION OF SYNCHRONOUS BILATERALRENAL TUMORS P. Dal Cin ~, H. Van PoppelL B. Van Damme 3, L. BaertL H. Van den Berghe ~ ~Centrum voor Menselijke Erfelijkheid, 2Department Urologie en 3Departement Pathologische Ontleedkunde, Katholieke Universiteit Leuven, Belgium
Cytogenetic investigations on synchronous bilateral renal tumors are scarce. We here report our findings on 13 renal tumors from 5 patients and review the literature. In bilateral as well as in solitary tumors, cytogenetic findings in each tumor correlated with the histological patterns i.e. combinations of trisomies for papillary renal cell carcinoma, loss of 3p-material for nonpapillary renal cell carcinoma, coincident loss of the Y chromosome and chromosome 1 in oncocytomas. Bilateral multifocal RCCs were always of the papillary type and the the karyotypes showed more or less the same numerical anomalies, with trisomies in different combinations in tumors within the same kidney as well as in both kidneys. Structural changes, in contrast, were different from tumor to tumor
Although the genetical changes occurring in Wilms tumor (an embryonal tumor of the kidney) have been investigated with cytogenetic and molecular techniques, there have been no reports up until now on comparative genomic hybridization (CGH) studies. In this study we applied a modified CGH protocol to analyze a series of ~47 Wilms tumors: labeled test and control DNA, Cot-I DNA and normal chromosomes were denatured simultaneously under a coverslip using a microwave. In our experience this method of denaturation has improved the intensity of the fluorescent signals and the morphology of the chromosomes. An additional advantage is that the quality of the CGH is no longer dependent on the batch of lymphocytes used to obtain the chromosome spreads. The majority of the tumors analyzed in this study had already been characterized by Southern analysis with markers from chromosomes i, 3p, 5q, 1 lp, 13q, 16q, 17p and 22q. These Southern data confirmed our CGH results. CGH analysis showed losses of lp, 4q, 7p, lip, 16q and 17p and gains of 1q, 7q, 8, 12q, 17q and 18. With the exception of loss of 4q all these chromosomal changes have been reported previously in studies using techniques other than CGH. However, the percentage of tumors showing loss of 11 p by CGH was strikingly lower than the percentage of tumors showing LOH of 1 Ip by Southern analysis. This can be explained by the fact that many Wilms tumors show uniparental disomy of I I p (as demonstrated with LOH studies in our series of tumors). ~63% of the tested tumors did not show any chromosomal losses or gains. Currently we are in the process of confirming losses found by CGH using microsatellite markers. Since our improved protocol has been proved to be a reliable routine technique for CGH analysis, we are using this technique to screen hepatoblastomas and rhabdomyosarcomas.