Genetic reflection of glioblastoma biopsy material in xenografts: characterization of 11 glioblastoma xenograft lines by comparative genomic hybridization

2000 ◽  
Vol 92 (4) ◽  
pp. 652-658 ◽  
Author(s):  
Judith W. M. Jeuken ◽  
Sandra H. E. Sprenger ◽  
Pieter Wesseling ◽  
Hans J. J. A. Bernsen ◽  
Ron F. Suijkerbuijk ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Tumor Biology ◽  
Point Of View ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Biopsy Material ◽  
Content Type ◽  
Chromosomal Imbalances ◽  
Fine Print

Object. Human tumors implanted as subcutaneous xenografts in nude mice are widely used for the study of tumor biology and therapy. Validation of these models requires knowledge of the genetic makeup of the xenografts. The aim of this study was to establish whether chromosomal imbalances in 11 xenograft lines derived from human glioblastomas multiforme (x-GBMs) are similar to those found in GBM biopsy samples. The authors also studied genetic stability during serial passaging of three xenograft lines.Methods. Chromosomal imbalances in x-GBMs were detected using comparative genomic hybridization (CGH). The authors compared the CGH results in x-GBMs with those in the original GBMs (o-GBMs) that were used to establish three of the xenograft lines and with the GBM biopsy results reported in the literature (l-GBMs). In three xenograft lines two different passages were analyzed.Conclusions. The results show that the chromosomal imbalances in x-GBMs are similar to those in o-GBMs and l-GBMs, indicating that the GBM xenograft lines used were valid models from a genetic point of view. The CGH analysis of two different passages of three xenograft lines indicates that x-GBMs (like l-GBMs) show intratumoral genetic heterogeneity and do not acquire chromosomal imbalances as a result of serial passaging.

Analysis of von Hippel—Lindau mutations with comparative genomic hybridization in sporadic and hereditary hemangioblastomas: possible genetic heterogeneity

2002 ◽  
Vol 97 (4) ◽  
pp. 977-982 ◽  
Author(s):  
Johanna M. M. Gijtenbeek ◽  
Bram Jacobs ◽  
Sandra H. E. Sprenger ◽  
Marc J. Eleveld ◽  
Ad Geurts van Kessel ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Molecular Mechanisms ◽  
Chromosome 3 ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Chromosome 3P ◽  
Chromosomal Imbalances ◽  
Fine Print

Object. Hemangioblastomas (HBs) occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. In the majority of VHL-related HBs, inactivation of the VHL tumor suppressor gene (TSG), which is located on chromosome 3p25–26, is found. The VHL gene is assumed to be involved also in the development of sporadic HBs. In a previous study of chromosomal aberrations of sporadic HBs, multiple chromosomal imbalances were found in the majority of tumors. The aim of this study was to analyze further both sporadic HBs and VHL-related HBs to determine if these histopathologically identical tumors have a different genetic background. Methods. Sixteen sporadic HBs and seven VHL-related HBs were identified by clinical criteria and analyzed. Comparative genomic hybridization was used to screen for chromosomal imbalances throughout the entire HB genome. Additionally, mutation analysis of the VHL gene was performed using direct sequencing. Loss of chromosome 3 and multiple other chromosomal imbalances were found in the sporadic HBs, although only one imbalance, a loss of chromosome 3, was detected in the seven VHL-related HBs. Somatic VHL gene mutations were found in one third of sporadic HBs, whereas a mutation of the VHL gene was detected in all VHL-related HBs. Conclusions. These results indicate that the molecular mechanisms underlying sporadic HBs and VHL-related HBs are different. Inactivation of the VHL gene is probably not the most important event in the tumorigenesis of sporadic HBs. Other mechanisms of inhibition of VHL protein function, or inactivation of other TSGs, on chromosome 3p or on other chromosomes, might be important in the development of sporadic HBs.

Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization

2002 ◽  
Vol 96 (3) ◽  
pp. 559-564 ◽  
Author(s):  
Judith W. M. Jeuken ◽  
Sandra H. E. Sprenger ◽  
Harry Vermeer ◽  
Arnoud C. Kappelle ◽  
Rudolf H. Boerman ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Malignant Progression ◽  
Comparative Genomic ◽  
Astrocytic Tumors ◽  
Genomic Hybridization ◽  
Content Type ◽  
Chromosomal Imbalances ◽  
Oligodendroglial Tumors ◽  
Recurrent Tumors ◽  
Fine Print

Object. Despite the rapid increase in knowledge concerning the genetic basis of malignant progression in astrocytic tumors, progression of oligodendroglial tumors (including both pure oligodendrogliomas and mixed oligoastrocytomas) is still poorly understood. The aim of the present study is the elucidation of chromosomal imbalances involved in the progression of oligodendroglial tumors toward malignancy. Methods. Using comparative genomic hybridization (CGH) on snap-frozen tumor tissue, the tumor genomes of five primary oligodendroglial tumors and associated recurrent tumors were screened for chromosomal imbalances. This information was correlated with clinical data (including follow-up data) and histopathological malignancy grade. In all cases an increase in chromosomal imbalances was detected in the recurrent tumor, indicating genetic progression. In three of the five cases this correlated with malignant progression detected at the histopathological level. The results indicate that, similar to what occurs in astrocytic tumors, chromosomal imbalances harboring genes involved in the cell proliferation control mechanism at the G1-S border are involved in the progression of oligodendroglial tumors. Additionally, although gains of genetic material on chromosome 7 and losses on chromosome 10 are most frequently detected in the course of malignant progression of astrocytic tumors, either or both of these can also occur during malignant progression of typical oligodendroglial tumors that contain losses involving chromosome 1p and/or chromosome 19q. Conclusions. When performed on optimally preserved material from a small set of primary oligodendroglial tumors and associated recurrent tumors, CGH detects chromosomal aberrations that potentially play a mechanistic role in the malignant progression of these tumors.

Comparative genomic hybridization analysis of craniopharyngiomas

2003 ◽  
Vol 98 (1) ◽  
pp. 162-164 ◽  
Author(s):  
Shlomit Rienstein ◽  
Eric F. Adams ◽  
David Pilzer ◽  
Ayala Aviram Goldring ◽  
Boleslaw Goldman ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Genetic Alterations ◽  
Genomic Alteration ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Dna Copy Number ◽  
Content Type ◽  
Fine Print

Object. Craniopharyngioma is the most common childhood brain tumor and is thought to arise from embryonic remnants of the Rathke pouch. Some craniopharyngiomas are monoclonal in origin and hence presumably harbor somatic genetic alterations, although the precise molecular mechanisms involved in craniopharyngioma development are unknown. The goal of this study was to identify genetic alterations in craniopharyngiomas. Methods. To gain insight into the molecular mechanisms involved in development of these tumors, the authors analyzed nine adamantinomatous craniopharyngiomas by using comparative genomic hybridization. Six tumors (67%) displayed at least one genomic alteration, and three had six or more alterations. Only two tumors displayed a decrease in DNA copy number, and in all others an increase in DNA copy number was noted. Conclusions. The authors conclude that a subset of craniopharyngiomas consists of monoclonal tumors arising from activation of oncogenes located at specific chromosomal loci.

Detection of chromosomal imbalances in central neurocytomas by using comparative genomic hybridization

2000 ◽  
Vol 93 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Xiao-Lu Yin ◽  
Jesse Chung-Sean Pang ◽  
Angela Bik-Yu Hui ◽  
Ho-Keung Ng
Keyword(s):  
Dna Sequence ◽  
Comparative Genomic Hybridization ◽  
Dna Sequences ◽  
Immunohistochemical Analysis ◽  
Comparative Genomic ◽  
Fluorescence Intensity Ratio ◽  
Genomic Hybridization ◽  
Metaphase Chromosomes ◽  
Content Type ◽  
Fine Print

Object. Central neurocytomas are rare neuronal tumors commonly found in the intraventricular regions. Little is known about the tumorigenesis of these neoplasms. The aim of this study was to provide an overview of genetic imbalances in central neurocytomas.Methods. In this study, comparative genomic hybridization was used to identify DNA sequence copy number changes (losses and gains) in a series of 10 central neurocytomas. Tumor DNA and normal reference DNA were differentially labeled and allowed to cohybridize to normal metaphase chromosomes. After hybridization and fluorescent staining of the bound DNA, regions of gain or of loss of DNA sequences were detected as changes in the tumor/normal fluorescence intensity ratio along the target metaphase chromosomes. A gain of DNA sequence was detected in chromosomes 2p, 10q, and 18q. A protooncogene, Bcl2, which maps to 18q21, was evaluated by immunohistochemical analysis to determine its role in the formation of central neurocytomas.Conclusions. In this study the authors identified recurrent genetic changes on chromosomes 2p, 10q, and 18q in central neurocytomas and highlighted chromosomal regions for additional mapping and cloning of candidate genes that are important in the development of central neurocytomas.

Multiple genetic aberrations including evidence of chromosome 11q13 rearrangement detected in pituitary adenomas by comparative genomic hybridization

1999 ◽  
Vol 90 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Andrew K. Metzger ◽  
Gayatry Mohapatra ◽  
Yuriko A. Minn ◽  
Andrew W. Bollen ◽  
Kathleen Lamborn ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Comparative Genomic Hybridization ◽  
Pituitary Adenomas ◽  
Genetic Material ◽  
Comparative Genomic ◽  
Chromosome 11 ◽  
Genomic Hybridization ◽  
Genetic Aberrations ◽  
Content Type ◽  
Fine Print

Object. This study was conducted to determine whether comparative genomic hybridization (CGH) is a more sensitive method for detecting genetic aberrations than other tests currently in use.Methods. The authors used CGH to examine 40 primary and 13 recurrent adenomas obtained from 52 patients for loss and gain of genetic material. Copy number aberrations (CNAs) were detected in 25 (48%) of the 52 patients studied. The chromosomes affected were, in order of decreasing frequency, 11, 7, X, 1, 8, 13, 5, 14, 2, 6, 9, 10, 12, 3, 18, 21, 4, 16, 15, 19, 22, and Y. Endocrinologically active adenomas were more likely to contain (p = 0.009) and had a greater number (p = 0.003) of CNAs. Of 26 adenomas with CNAs, 18 showed multiple aberrations involving entire chromosomes or chromosome arms. The most frequent CNA involving a chromosome subregion, which was present in four (8%) of 53 adenomas, was the loss of all chromosome 11 material except for a preserved common segment containing 11q13. Immunoperoxidase staining did not detect cyclin D1 expression in those four cases, making cyclin D1 an unlikely target of this rearrangement.Conclusions. These findings indicate that genetic abnormalities are present in pituitary adenomas at a higher rate than previously reported, are associated with endocrinological activity, and often involve several chromosomes. Rearrangement at 11q13 may inactivate a tumor suppressor gene or activate an oncogene that is important in the initiation or progression of sporadic pituitary adenomas.

Analysis of chromosomal imbalances in de novo CD5-positive diffuse large-B-cell lymphoma detected by comparative genomic hybridization

2003 ◽  
Vol 39 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Sivasundaram Karnan ◽  
Hiroyuki Tagawa ◽  
Ritsuro Suzuki ◽  
Miyuki Suguro ◽  
Motoko Yamaguchi ◽  
...  
Keyword(s):  
B Cell ◽  
Comparative Genomic Hybridization ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Chromosomal Imbalances ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization

2001 ◽  
Vol 127 (1) ◽  
pp. 49-52 ◽  
Author(s):  
M.A Collonge-Rame ◽  
S Bresson-Hadni ◽  
S Koch ◽  
J.P Carbillet ◽  
O Blagosklonova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Comparative Genomic Hybridization ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Chromosomal Imbalances ◽  
B Virus
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