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DNA deletion mapping in meningioma by pulsed field gel electrophoresis
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Abstracts
49
KARYOTYPE PATTERN AND TUMORAL AGGRESSIVENESS IN HUMAN MENINGIOMAS. J. M. de Campos*; M. E. Kusak*; J. A. Reyt", M. J. Belle1"; S. Morenot; P. Ruiz Barn~s*. Departments of Neurosurgery* and Genetics,'[" Fundaci6n Jim6nez Dlaz, Madrid, Spain
In order to establish a correlation between tumoral aggressiveness and cytogenetic findings, clinico-pathological features and long term follow-up have been reviewed in a series of 32 patients operated on for meningioma, whose tumor cell karyotypes had been studied. Since 4 patients died from postoperative complications, they are not included for follow-up evaluation. Eight normal diploid tumors, 10 with monosomy 22 as sole anomaly, and 3 with other anomalies not affecting pair 22 had a typical benign histopathological appearance, and the patients are free of recurrence after a 30-81 me. follow-up (median 53 months). Two of these patients, who underwent a subtotal tumor removal, are free of progression after 60 me. Five of 11 cases with monosomy 22 plus other numerical and/or structural abnormalities had one or more characteristics of tumoral aggressiveness: Short-term recurrence (1 case), atypical histopathological features (4 cases), or they were recurrences of a previous tumor (3 cases). No other relations among cytogenetic findings and clinical or histopathological characteristics could be found. These results suggest that tumor chromosomal analysis can be helpful in determining the prognosis in meningiomas. Patients with " - 2 2 plus other" tumor karyotype pattern should be considered for eventual recurrences.
50
SPECTRUM OF KARYOTYPIC ABERRATIONS IN CULTURED HUMAN MENINGIOMAS. Manfred Westphal, Marianne Hansel, Regina Kunzman*, Fritz H61zel*, and Hans-Dietrich Herrmann. Department of Neurological Surgery and Department of Physiological Chemistry and Molecular Biology (*), University Hospital Eppendorf, 2000 Hamburg 20, F.R.G.
Twenty.two meningiomas were initiated in tissue culture on an extracellular matrix derived from bovine corneal endothelial cells, and available for karyotypic analysis in passage I to 11 (mostly I to 5) representing culture periods of up to two months. Histologically, the meningiomas were meningiotheliomatous (16 cases), fibrous/parenchymatous (3 cases), angiotheliomatous (1 case) and microcystic (2 cases). Two of the meningiotheliomatous cases showed histological signs of malignancy, another case showed increased signs of in vivo proliferation. Two cases were from recurrent meningiomas, one after a complete course of irradiation. Monosomy chromosome 22 was found in 6 cases and was present in all metaphases, In all these cases, monosomy 22 was associated with other random aberrations. Clonal or random aberrations without monosomy 22 were present in 7 cases, including one case with trisomy 7 and another case with a stable translocation marker t(4~7), In these latter cases EGF-receptor binding was within the range expected in maningiomas. In contrast to gliomas in which an increase in chromosome ? bearing the EGF-receptor gene has been suggested to be related to their proliferative behavior, trisomy 7 did not confer a growth advantage to the cultured meningioma ce~ls. Most of our cultured maningiomas had a life span limited to 10 to 12 in vitro passages, The results illustrate that in addition to the frequent involvement of chromosome 22 in aberrations other individual clonal aberrations exist in meningiomas, reflecting the heterogeneity of biological and pathological findings.
51
DNA DELETION MAPPING IN MENINGIOMA BY PULSED HELD GEL ELECTROPHORESIS. R. Herzog I, E. Mease2, K. D. Zang1, J. Trent2, N. Blin!. ~Human Genetics, University of the Sear, Homburg, F.R.G., ZArizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Suppression of the tumorigenic phenotype of tumor cells can be experimentally achieved when malignant cells are fused with normal cells. Particular chromosomal loci have been suspected in regulating this process. Recently, by using chromosome specific polymorphic DNA probes, deletions of such supposed tumor suppressor genes were demonstrated in several human solid tumors, e.g. retinoblastoma, renal cell carcinoma etc. In some neuroectodermal tumors, loss of alleles of particular loci mapped to chromosome 22 was reported (pheochromocytoma, acoustic neurinoma, maningioma), however, without specifying a singular gene sequence. By applying long range mdl~ping of chromosome 22 by means of pulsed-field gel electrophoresis and chromosome 22 specific DNA markers (D22S16, PDGFB) we have attempted to characterize the domain of DNA loss in more detail. For this purpose, meningioma primary cell cultures displaying a regular complement of chromosomes (n = 46) were used. Genomic DNA from normal and tumor cells was fractionated using "rare cutter" endonucleases and restriction patterns were recorded by autorediography. Partial digests and coupling of applied enzymes are now being used to construct a long range restriction map.
Abstracts
49
KARYOTYPE PATTERN AND TUMORAL AGGRESSIVENESS IN HUMAN MENINGIOMAS. J. M. de Campos*; M. E. Kusak*; J. A. Reyt", M. J. Belle1"; S. Morenot; P. Ruiz Barn~s*. Departments of Neurosurgery* and Genetics,'[" Fundaci6n Jim6nez Dlaz, Madrid, Spain
In order to establish a correlation between tumoral aggressiveness and cytogenetic findings, clinico-pathological features and long term follow-up have been reviewed in a series of 32 patients operated on for meningioma, whose tumor cell karyotypes had been studied. Since 4 patients died from postoperative complications, they are not included for follow-up evaluation. Eight normal diploid tumors, 10 with monosomy 22 as sole anomaly, and 3 with other anomalies not affecting pair 22 had a typical benign histopathological appearance, and the patients are free of recurrence after a 30-81 me. follow-up (median 53 months). Two of these patients, who underwent a subtotal tumor removal, are free of progression after 60 me. Five of 11 cases with monosomy 22 plus other numerical and/or structural abnormalities had one or more characteristics of tumoral aggressiveness: Short-term recurrence (1 case), atypical histopathological features (4 cases), or they were recurrences of a previous tumor (3 cases). No other relations among cytogenetic findings and clinical or histopathological characteristics could be found. These results suggest that tumor chromosomal analysis can be helpful in determining the prognosis in meningiomas. Patients with " - 2 2 plus other" tumor karyotype pattern should be considered for eventual recurrences.
50
SPECTRUM OF KARYOTYPIC ABERRATIONS IN CULTURED HUMAN MENINGIOMAS. Manfred Westphal, Marianne Hansel, Regina Kunzman*, Fritz H61zel*, and Hans-Dietrich Herrmann. Department of Neurological Surgery and Department of Physiological Chemistry and Molecular Biology (*), University Hospital Eppendorf, 2000 Hamburg 20, F.R.G.
Twenty.two meningiomas were initiated in tissue culture on an extracellular matrix derived from bovine corneal endothelial cells, and available for karyotypic analysis in passage I to 11 (mostly I to 5) representing culture periods of up to two months. Histologically, the meningiomas were meningiotheliomatous (16 cases), fibrous/parenchymatous (3 cases), angiotheliomatous (1 case) and microcystic (2 cases). Two of the meningiotheliomatous cases showed histological signs of malignancy, another case showed increased signs of in vivo proliferation. Two cases were from recurrent meningiomas, one after a complete course of irradiation. Monosomy chromosome 22 was found in 6 cases and was present in all metaphases, In all these cases, monosomy 22 was associated with other random aberrations. Clonal or random aberrations without monosomy 22 were present in 7 cases, including one case with trisomy 7 and another case with a stable translocation marker t(4~7), In these latter cases EGF-receptor binding was within the range expected in maningiomas. In contrast to gliomas in which an increase in chromosome ? bearing the EGF-receptor gene has been suggested to be related to their proliferative behavior, trisomy 7 did not confer a growth advantage to the cultured meningioma ce~ls. Most of our cultured maningiomas had a life span limited to 10 to 12 in vitro passages, The results illustrate that in addition to the frequent involvement of chromosome 22 in aberrations other individual clonal aberrations exist in meningiomas, reflecting the heterogeneity of biological and pathological findings.
51
DNA DELETION MAPPING IN MENINGIOMA BY PULSED HELD GEL ELECTROPHORESIS. R. Herzog I, E. Mease2, K. D. Zang1, J. Trent2, N. Blin!. ~Human Genetics, University of the Sear, Homburg, F.R.G., ZArizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Suppression of the tumorigenic phenotype of tumor cells can be experimentally achieved when malignant cells are fused with normal cells. Particular chromosomal loci have been suspected in regulating this process. Recently, by using chromosome specific polymorphic DNA probes, deletions of such supposed tumor suppressor genes were demonstrated in several human solid tumors, e.g. retinoblastoma, renal cell carcinoma etc. In some neuroectodermal tumors, loss of alleles of particular loci mapped to chromosome 22 was reported (pheochromocytoma, acoustic neurinoma, maningioma), however, without specifying a singular gene sequence. By applying long range mdl~ping of chromosome 22 by means of pulsed-field gel electrophoresis and chromosome 22 specific DNA markers (D22S16, PDGFB) we have attempted to characterize the domain of DNA loss in more detail. For this purpose, meningioma primary cell cultures displaying a regular complement of chromosomes (n = 46) were used. Genomic DNA from normal and tumor cells was fractionated using "rare cutter" endonucleases and restriction patterns were recorded by autorediography. Partial digests and coupling of applied enzymes are now being used to construct a long range restriction map.