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Characterization of chromosome 12 anomalies in human germ cell tumors
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PATHOGENESIS OF RENAL CELL CYTOGENETIC MODEL. Eva van
Abstracts
TUMORS:
A
den Berq, Wolter 0osterhuis, Stephan St6rkel, Trijnie Dijkhuizen, Anke Dam, Han Mensink, Bauke de Jong, Depts. of Medical Genetics, Pathology and Urology, Ant. Deusinglaan 4, 9713 A W Groningen, Rotterdam, The Netherlands and Mainz, Germany. Renal cell cancers (RCC) are epithelial neoplasms demonstrating a diversity of morphologic characteristics and clinical manifestations. About 14% of the RCC are chromophilic and 75% are of the clear cell type, 3% of the RCC are mixed tumors of the clear cell and chromophilic type. To date there are no really distinct criteria to reliably distinguish renal adenomas from carcinomas. About 99% of renal adenomas are chromophilic, no clear cell adenomas can be found. So one might ask whether there is no relationship between renal cell adenomas and carcinomas, or whether there is progression from adenomas to chromophilic carcinomas to clear cell carcinomas. The chromosomal pattern of the different types of tumors, especially of the different parts of mixed tumors might reveal this relationship and progression model. Based on our (cyto)genetic and pathological study of a large sample of renal cell tumors, as well as in the accumulated data in the literature, we propose a new model of pathogenesis of renal cell tumors.
FINE MAPPING OF THE HUMAN RENAL ONCOCYTOMA-ASSOC1ATED t(5;ll) CHROMOSOMAL BREAKPOINT IN 1 lq13 A. Geurts van Kes~l ~, D. Olde Weghuis ~, R.J. Sinke ~, H.A.P. Jaassen I, T. Dijkhuizen 2, A. Dam 3, H.J.A. Mensink 4, J.W. Oosterhui~~, 13. de Jong2 and E. van den Berg-de Ruiter< ~Department of Human Genetics, University Hospital Nijmegen, 2Department of Medical Genetics, University of Groningen, 3Department of Pathology, University of Groningen, ~Department of Urology, University of Groningen, 5Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. Renal oncocytomas represent a group of primary tumors of the kidney whose hallmark is the presence of the 'oncocytic cell', an epithelial cell with a strongly eosinophilic and intensely granular cytoplasm. Oncoeytomas account for about 5% of all renal tumors. The pathogenetic relationship with other renal neoplasias is still a matter of debate. At the genetic level, renal oncocytomas are marked by alterations in their mitochondrial DNA and by lack of rearrangements of chromosome 3p which, in contrast, are frequently encountered in renal cell carcinomas. These observations indicate that the oncocytomas constitute a distinct class of renal neoplasms. Recent cytogenetic analysis of a series of renal tumors revealed the presence of a t(5;ll)(q35;q13) as sole chromosomal anomaly in a subset of oncocytomas [1]. This latter observation suggests that this t(5;ll) transloeation may define a specific class of renal tumors. In addition, it is assumed that the unique character of the translocation may be indicative for a causel role in tumor development. Therefore, we set out to characterize the (5;11) translocation in detail starting out from the llq13 region, using both translocation chromosome-containing somatic cell hybrids in conjunction with Southern blot analysis and fluorescence in situ hybridization (FISH) on primary tumor matrial employing 1 lq13 bandspecific eosmids. Details of the results obtained and comparisons with other tumor-specific 1 lq13 anomalies will be presented. [1[ van den Berg-de Ruiter E. et al. Chromo~mal Oncocytomas: Thesis 57-64 (1993).
Changes in Renal
CHARACTERIZATION OF CHROMOSOME 12 ANOMALIES IN HUMAN GERM CELL TUMORS. R.F. Suiikerbuiik ~, R.J. Sinke ~, A.M. Meloni 2, J.M. Parrington 3, J. van Eehten 4, B. de Jong 4, J.W. Oosterhuis ~, S. Castedo ~, L. Roque 7, G. Soares 7, A.A. Sandberg 2, and A. Geurts van Kessel t LDepartment of Human Genetics, University Hospital, Nijmegen, The Netherlands Vl'he Cancer Center and the Genetics Center, Genetrix, Scottsdale, AZ, USA YI'he Galtoo Laboratory, University College, London, UK 4Department of Medical Genetics, University of Groningen, The Netherlands 5Daniel den Hoed Cancer Center, Rotterdam, The Netherlands ~Department of Genetics, IPATIMUP, Hospital de S. Joao, Porto, Portugal ~Department of Morphological Pathology, IPOFG, Lisboa, Portugal Human testicular germ cell tumors (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumors are characterized by the presence of a highly specific chromosomal abnormality, i.e., an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome is found in more than 80% of TGCTs. l(12p) has also been observed in some ovarian and extragonadal germ cell tumors. In the remaining so called i(12p)-negative TGCTs other abnormalities involving chromosome 12, mainly 12p, can be found [1,2]. In order to establish whether 12p abnormalities other than i(12p) are a common characteristic of TGCTs, a panel of twelve i(12p)-negative tumors was investigated using multicolor fluorescence in situ hybridization. All TGCTs examined appeared to contain chromosomal abnormalities involving 12p, resulting in a distinct overrepresentation of short arm sequences. In one of these tumors this overrepresentation appeared to be confined to a specific subregion (amplicon) of 12p. In addition, indications were obtained for a clonal evolution in one of the tumors. Our data suggest that the occurrence of 12p abnormalities is a common characteristic of i(12p)-negative TGCTs and that these abnormalities, analogous to i(12p), may contribute to the process of tumor development. Rare tumor cases, as those containing amplicons, may finally reveal the critical genomic sequences involved. The identification and putative role of amplicon-associated gene(s) will be discussed in detail. [1] Suijkerbuijk, R.F. et al., Am. J. Hum. Genet. 48:269-273 (1991) [2] Suijkerbuijk, R.F. et al., Cancer Genet. Cytogenet. 63:8-16 (1992)
CYTOGENETIC ABERRATIONS OF CHROMOSOME 12 IN HUMAN SOLID TUMORS. Nils Mandahl, Department of Clinical Genetics, University Hospital, S-221 85 Lund, Sweden. Chromosome 12 is involved in several nonrandom aberrations in human solid tumors, in particular in mesenchymal tumors. Among the structural chromosome 12 aberrations there is a breakpoint clustering to chromosome segment 12q13-15. These rearrangements include t(12;16) (ql3;pll) in myxoid liposarcoma and t(12;22) (q13;q12) in clear cell sarcoma of tendons and aponeuroses. Various translocations between 12q13-15 and several other bands are frequently found in lipomas, uterine leiomyomas, and pleomorphic adenomas of the salivary gland, with a preferential involvement of 3q27-28, 14q23-24, and 9p21-24, respectively. Trisomy 12 characterizes another cytogenetic subgroup of leiomyomas. Aberrations involving 12q13-15 have also been found in subsets of chondromas, hemangiopericytomas, hamartomas of the lung, and endometrial polyps. The karyotypic profiles, with respect to structural and numerical changes of chromosome 12, in all major histotypes of mesenchymal tumors and, in less detail, in other solid tumors, will be reviewed.
PATHOGENESIS OF RENAL CELL CYTOGENETIC MODEL. Eva van
Abstracts
TUMORS:
A
den Berq, Wolter 0osterhuis, Stephan St6rkel, Trijnie Dijkhuizen, Anke Dam, Han Mensink, Bauke de Jong, Depts. of Medical Genetics, Pathology and Urology, Ant. Deusinglaan 4, 9713 A W Groningen, Rotterdam, The Netherlands and Mainz, Germany. Renal cell cancers (RCC) are epithelial neoplasms demonstrating a diversity of morphologic characteristics and clinical manifestations. About 14% of the RCC are chromophilic and 75% are of the clear cell type, 3% of the RCC are mixed tumors of the clear cell and chromophilic type. To date there are no really distinct criteria to reliably distinguish renal adenomas from carcinomas. About 99% of renal adenomas are chromophilic, no clear cell adenomas can be found. So one might ask whether there is no relationship between renal cell adenomas and carcinomas, or whether there is progression from adenomas to chromophilic carcinomas to clear cell carcinomas. The chromosomal pattern of the different types of tumors, especially of the different parts of mixed tumors might reveal this relationship and progression model. Based on our (cyto)genetic and pathological study of a large sample of renal cell tumors, as well as in the accumulated data in the literature, we propose a new model of pathogenesis of renal cell tumors.
FINE MAPPING OF THE HUMAN RENAL ONCOCYTOMA-ASSOC1ATED t(5;ll) CHROMOSOMAL BREAKPOINT IN 1 lq13 A. Geurts van Kes~l ~, D. Olde Weghuis ~, R.J. Sinke ~, H.A.P. Jaassen I, T. Dijkhuizen 2, A. Dam 3, H.J.A. Mensink 4, J.W. Oosterhui~~, 13. de Jong2 and E. van den Berg-de Ruiter< ~Department of Human Genetics, University Hospital Nijmegen, 2Department of Medical Genetics, University of Groningen, 3Department of Pathology, University of Groningen, ~Department of Urology, University of Groningen, 5Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. Renal oncocytomas represent a group of primary tumors of the kidney whose hallmark is the presence of the 'oncocytic cell', an epithelial cell with a strongly eosinophilic and intensely granular cytoplasm. Oncoeytomas account for about 5% of all renal tumors. The pathogenetic relationship with other renal neoplasias is still a matter of debate. At the genetic level, renal oncocytomas are marked by alterations in their mitochondrial DNA and by lack of rearrangements of chromosome 3p which, in contrast, are frequently encountered in renal cell carcinomas. These observations indicate that the oncocytomas constitute a distinct class of renal neoplasms. Recent cytogenetic analysis of a series of renal tumors revealed the presence of a t(5;ll)(q35;q13) as sole chromosomal anomaly in a subset of oncocytomas [1]. This latter observation suggests that this t(5;ll) transloeation may define a specific class of renal tumors. In addition, it is assumed that the unique character of the translocation may be indicative for a causel role in tumor development. Therefore, we set out to characterize the (5;11) translocation in detail starting out from the llq13 region, using both translocation chromosome-containing somatic cell hybrids in conjunction with Southern blot analysis and fluorescence in situ hybridization (FISH) on primary tumor matrial employing 1 lq13 bandspecific eosmids. Details of the results obtained and comparisons with other tumor-specific 1 lq13 anomalies will be presented. [1[ van den Berg-de Ruiter E. et al. Chromo~mal Oncocytomas: Thesis 57-64 (1993).
Changes in Renal
CHARACTERIZATION OF CHROMOSOME 12 ANOMALIES IN HUMAN GERM CELL TUMORS. R.F. Suiikerbuiik ~, R.J. Sinke ~, A.M. Meloni 2, J.M. Parrington 3, J. van Eehten 4, B. de Jong 4, J.W. Oosterhuis ~, S. Castedo ~, L. Roque 7, G. Soares 7, A.A. Sandberg 2, and A. Geurts van Kessel t LDepartment of Human Genetics, University Hospital, Nijmegen, The Netherlands Vl'he Cancer Center and the Genetics Center, Genetrix, Scottsdale, AZ, USA YI'he Galtoo Laboratory, University College, London, UK 4Department of Medical Genetics, University of Groningen, The Netherlands 5Daniel den Hoed Cancer Center, Rotterdam, The Netherlands ~Department of Genetics, IPATIMUP, Hospital de S. Joao, Porto, Portugal ~Department of Morphological Pathology, IPOFG, Lisboa, Portugal Human testicular germ cell tumors (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumors are characterized by the presence of a highly specific chromosomal abnormality, i.e., an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome is found in more than 80% of TGCTs. l(12p) has also been observed in some ovarian and extragonadal germ cell tumors. In the remaining so called i(12p)-negative TGCTs other abnormalities involving chromosome 12, mainly 12p, can be found [1,2]. In order to establish whether 12p abnormalities other than i(12p) are a common characteristic of TGCTs, a panel of twelve i(12p)-negative tumors was investigated using multicolor fluorescence in situ hybridization. All TGCTs examined appeared to contain chromosomal abnormalities involving 12p, resulting in a distinct overrepresentation of short arm sequences. In one of these tumors this overrepresentation appeared to be confined to a specific subregion (amplicon) of 12p. In addition, indications were obtained for a clonal evolution in one of the tumors. Our data suggest that the occurrence of 12p abnormalities is a common characteristic of i(12p)-negative TGCTs and that these abnormalities, analogous to i(12p), may contribute to the process of tumor development. Rare tumor cases, as those containing amplicons, may finally reveal the critical genomic sequences involved. The identification and putative role of amplicon-associated gene(s) will be discussed in detail. [1] Suijkerbuijk, R.F. et al., Am. J. Hum. Genet. 48:269-273 (1991) [2] Suijkerbuijk, R.F. et al., Cancer Genet. Cytogenet. 63:8-16 (1992)
CYTOGENETIC ABERRATIONS OF CHROMOSOME 12 IN HUMAN SOLID TUMORS. Nils Mandahl, Department of Clinical Genetics, University Hospital, S-221 85 Lund, Sweden. Chromosome 12 is involved in several nonrandom aberrations in human solid tumors, in particular in mesenchymal tumors. Among the structural chromosome 12 aberrations there is a breakpoint clustering to chromosome segment 12q13-15. These rearrangements include t(12;16) (ql3;pll) in myxoid liposarcoma and t(12;22) (q13;q12) in clear cell sarcoma of tendons and aponeuroses. Various translocations between 12q13-15 and several other bands are frequently found in lipomas, uterine leiomyomas, and pleomorphic adenomas of the salivary gland, with a preferential involvement of 3q27-28, 14q23-24, and 9p21-24, respectively. Trisomy 12 characterizes another cytogenetic subgroup of leiomyomas. Aberrations involving 12q13-15 have also been found in subsets of chondromas, hemangiopericytomas, hamartomas of the lung, and endometrial polyps. The karyotypic profiles, with respect to structural and numerical changes of chromosome 12, in all major histotypes of mesenchymal tumors and, in less detail, in other solid tumors, will be reviewed.