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Arie Perry - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 22q deletions in atypical teratoid rhabdoid tumors in adults
Brain Pathology, 2006Co-Authors: Jack M Raisanen, Jaclyn A Biegel, Kimmo J Hatanpaa, Alexander R Judkins, Charles L White, Arie PerryAbstract:Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the IN11/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45. Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of Chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults.
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Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults
Brain Pathology, 2006Co-Authors: Jack M Raisanen, Jaclyn A Biegel, Kimmo J Hatanpaa, Alexander R Judkins, Charles L White, Arie PerryAbstract:Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the IN11/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45. Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of Chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults.
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Chromosome 22q dosage in composite extrarenal rhabdoid tumors clonal evolution or a phenotypic mimic
Human Pathology, 2001Co-Authors: Christine E Fuller, John D Pfeifer, Peter A Humphrey, Leslie A Bruch, Louis P Dehner, Arie PerryAbstract:Abstract Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior. Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other Chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant ( P
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Chromosome 22q dosage in composite extrarenal rhabdoid tumors : Clonal evolution or a phenotypic mimic ?
Human Pathology, 2001Co-Authors: Christine E Fuller, John D Pfeifer, Peter A Humphrey, Leslie A Bruch, Louis P Dehner, Arie PerryAbstract:Abstract Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior. Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other Chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant ( P
Ian G Campbell - One of the best experts on this subject based on the ideXlab platform.
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Genetic and epigenetic analysis of the TIMP-3 gene in ovarian cancer
Cancer Letters, 2006Co-Authors: David Y.h. Choong, Christine S. F. Hooi, Louise H. Williams, Ian G CampbellAbstract:Chromosome 22q shows a high frequency of loss of heterozygosity (LOH) in ovarian cancers suggesting the existence of one or more important tumor suppressor genes (TSGs). The tissue inhibitor of metalloproteinase-3 (TIMP-3) is a plausible TSG candidate since it is often encompassed within these regions of LOH. TIMP-3 has not previously been investigated for somatic mutations or promoter hypermethylation in ovarian cancer. We analyzed 65 ovarian cancers for both somatic genetic mutations and TIMP-3 promoter hypermethylation. Screening of all coding exons of TIMP-3 did not reveal any somatic genetic mutations and only 1/65 showed TIMP-3 methylation. Our data indicate that inactivation of TIMP-3 by somatic mutation or promoter hypermethylation is rare in ovarian cancer.
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refinement of an ovarian cancer tumour suppressor gene locus on Chromosome arm 22q and mutation analysis of cyp2d6 srebp2 and naga
International Journal of Cancer, 2000Co-Authors: Emma J Bryan, Nicola A Thomas, Karan Palmer, Elisabeth Dawson, Patricia Englefield, Ian G CampbellAbstract:Loss of heterozygosity on Chromosome 22q was detected in 53% of 123 ovarian carcinomas, suggesting the presence of at least one tumour suppressor gene. We have refined the location of one possible tumour suppressor gene to the region between the microsatellite markers D22S299 and CYP2D. Located within this region are the genes SREBP2 (sterol regulatory element binding protein 2) and NAGA (N-acetyl-alpha-D-galactosaminidase). Investigation of the coding exons of these genes by single stranded conformational polymorphism/heteroduplex analysis failed to identify any somatic genetic alterations in 57 ovarian tumours which exhibited LOH on 22q13. The CYP2D gene locus straddles the distal boundary of the candidate region. Germline variants of the active CYP2D6 gene with differing abilities to metabolise specific substrates have been implicated in the development of various cancers. Comparison of the frequency of the two common germline mutations among 258 ovarian tumours and 231 non-cancer controls did not reveal any significant differences between the two groups. This suggests that the known polymorphic variants of CYP2D6 are not involved in ovarian cancer predisposition. We also conclude that neither NAGA nor SREBP2 are likely to be mutated in ovarian carcinomas. Int. J. Cancer 87:798–802, 2000. © 2000 Wiley-Liss, Inc.
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localization of an ovarian cancer tumor suppressor gene to a 0 5 cm region between d22s284 and cyp2d on Chromosome 22q
Cancer Research, 1996Co-Authors: Emma J Bryan, Richard H Watson, Michael Davis, Andrew Hitchcock, William D Foulkes, Ian G CampbellAbstract:The detection of loss of heterozygosity, indicative of the presence of a tumor suppressor gene, has been reported to occur frequently on Chromosome 22q in human ovarian cancer. In this study, 110 sporadic ovarian tumors were analyzed using 8 polymorphic loci to define a minimum region of loss. Fifty-eight (53%) tumors showed loss of heterozygosity, and of these 6 exhibited partial loss, enabling the identification of two candidate tumor suppressor gene loci. One region, of less than 0.5 cM, is flanked by D22S284 and CYP2D , and a second region lies distal to D22S276 . Analysis of loss of heterozygosity with respect to grade and stage suggests that Chromosome 22q loss of heterozygosity is of more relevance in tumor progression rather than initiation.
Christine E Fuller - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 22q dosage in composite extrarenal rhabdoid tumors clonal evolution or a phenotypic mimic
Human Pathology, 2001Co-Authors: Christine E Fuller, John D Pfeifer, Peter A Humphrey, Leslie A Bruch, Louis P Dehner, Arie PerryAbstract:Abstract Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior. Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other Chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant ( P
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Chromosome 22q dosage in composite extrarenal rhabdoid tumors : Clonal evolution or a phenotypic mimic ?
Human Pathology, 2001Co-Authors: Christine E Fuller, John D Pfeifer, Peter A Humphrey, Leslie A Bruch, Louis P Dehner, Arie PerryAbstract:Abstract Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior. Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other Chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant ( P
Andreas Von Deimling - One of the best experts on this subject based on the ideXlab platform.
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fine mapping of Chromosome 22q tumor suppressor gene candidate regions in astrocytomas
International Journal of Cancer, 2004Co-Authors: Christian Hartmann, Astrid Numann, Wolf Mueller, Nikola Holtkamp, Matthias Simon, Andreas Von DeimlingAbstract:Astrocytomas and glioblastomas are the most frequent primary brain tumors in adults. Mutations and altered expression of multiple genes have been found to contribute to the genesis of these tumors. However, many factors in the genesis of astrocytic gliomas are not resolved yet. The frequent losses on several Chromosomes indicate the role of still unidentified tumor suppressor genes. Loss of heterozygosity (LOH) on 22q has been described in up to 30% of astrocytic tumors and may be associated with progression to anaplasia. In a first step, information from the nearly finished physical sequence of Chromosome 22 were used to map LOH data from 22q deletion studies on different tumor entities to identify potential tumor suppressor gene candidate regions. Next, a series of 153 astrocytic gliomas was examined with 11 polymorphic markers spanning these regions. Forty-nine (32%) astrocytic gliomas exhibited LOH on 22q, 17 (35%) of which lost heterozygosity for all markers and 32 (65%) of which carried interstitial or partial deletions. Two regions were identified on the physical DNA sequence. The centromeric region spans 3 Mb and the telomeric region 2.7 Mb. The reduced size of these regions now allows direct analysis of all genes included. We already performed mutation analysis on 4 candidate genes from these regions (MYO18B, DJ1042K10.2, MKL1 and EP300), but did not find any mutations in astrocytic tumors. © 2003 Wiley-Liss, Inc.
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Common regions of deletion on Chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade.
Journal of Neuropathology and Experimental Neurology, 1999Co-Authors: Jonathan S. Silver, Lisa Blazejewski, Ryo Nishikawa, Masao Matsutani, Andreas Von Deimling, David N. LouisAbstract:Approximately 30% of human astrocytomas have been reported to display allelic loss of the long arm of Chromosome 22, suggesting the presence of a Chromosome 22q astrocytoma suppressor gene. To define the most likely location for this putative tumor suppressor, we performed deletion mapping on 141 tumors using 16 Chromosome 22q microsatellite markers. Allelic loss of 22q was observed in 2/12 (17%) of astrocytomas, 9/29 (31%) of anaplastic astrocytomas, and 38/100 (38%) of glioblastomas, consistent with a role for Chromosome 22q loss in astrocytoma progression as well as formation. Twenty-two tumors exhibited allelic loss at every informative locus, consistent with loss of the entire arm of 22q. Twenty-seven tumors showed partial deletions, with one common region of deletion at 22q12.3-q13.1 between markers D22S280 and D22S282, and a second candidate region at 22q13.2 near the marker D22S1170. For the proximal candidate region, the incidence of allelic loss was similar between grades; for the distal locus, the incidence increased with grade, raising the possibility that the distal locus is involved in a later stage of astrocytoma tumorigenesis.
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molecular genetic analysis of ependymal tumors nf2 mutations and Chromosome 22q loss occur preferentially in intramedullary spinal ependymomas
American Journal of Pathology, 1999Co-Authors: Christian Ebert, Markus Von Haken, Birgit Meyerputtlitz, Otmar D Wiestler, Guido Reifenberger, Torsten Pietsch, Andreas Von DeimlingAbstract:Ependymal tumors are heterogeneous with regard to morphology, localization, age at first clinical manifestation, and prognosis. Several molecular alterations have been reported in these tumors, including allelic losses on Chromosomes 10, 17, and 22 and mutations in the NF2 gene. However, in contrast to astrocytic gliomas, no consistent molecular alterations have been associated with distinct types of ependymal tumors. To evaluate whether morphological subsets of ependymomas are characterized by specific genetic lesions, we analyzed a series of 62 ependymal tumors, including myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic ependymomas, for allelic losses on Chromosome arms 10q and 22q and mutations in the PTEN and NF2 genes. Allelic losses on 10q and 22q were detected in 5 of 56 and 12 of 54 tumors, respectively. Six ependymomas carried somatic NF2 mutations, whereas no mutations were detected in the PTEN gene. All six of the NF2 mutations occurred in ependymomas of WHO grade II and were exclusively observed in tumors with a spinal localization (P = 0.0063). These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving Chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis. Furthermore, our data suggest that the more favorable clinical course of spinal ependymomas may relate to a distinct pattern of genetic alterations different from that of intracerebral ependymomas.
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Analysis of the Neurofibromatosis 2 Gene in Human Ependymomas and Astrocytomas
Cancer Research, 1994Co-Authors: Mari Paz Rubio, Vijaya Ramesh, James F. Gusella, Andreas Von Deimling, Katia M. Correa, Mia Maccollin, Lee B. Jacoby, David N. LouisAbstract:Ependymomas and astrocytomas commonly have allelic losses of Chromosome 22q, which suggests the presence of a glioma tumor suppressor gene on 22q. A candidate tumor suppressor gene on 22q is the neurofibromatosis 2 ( NF2 ) gene since NF2 patients have an increased susceptibility to ependymomas and astrocytomas. Using single strand conformation polymorphism analysis and direct DNA sequencing, we screened 8 ependymomas and 30 fibrillary astrocytomas from non-NF2 patients for mutations in the coding sequence and portions of the 3′ untranslated region of the NF2 gene. Only one mutation was detected, a single base deletion in NF2 exon 7 from a spinal ependymoma, which had also lost the wild-type allele. These results suggest that the NF2 gene may be important in the formation of some ependymomas but the NF2 gene is probably not the critical Chromosome 22q tumor suppressor gene involved in astrocytoma tumorigenesis.
Detlef K Bartsch - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 22q in pancreatic endocrine tumors identification of a homozygous deletion and potential prognostic associations of allelic deletions
European Journal of Endocrinology, 2002Co-Authors: Anja Wild, P Langer, Brunhilde Chaloupka, I Celik, Detlef K BartschAbstract:Objective: A variety of human tumors frequently show allelic deletions of Chromosome 22q, suggesting that inactivation of one or more tumor suppressor genes in this region is important for their tumorigenesis. Methods: In this study, 23 patients with pancreatic endocrine tumors (PETs), including gastrinomas, VIPomas and non-functioning islet cell carcinomas, were analyzed for loss of heterozygosity (LOH) on Chromosome 22q with 12 microsatellite and 7 sequence tagged site markers. Results: LOH on Chromosome 22q was identified in 22 of 23 (96%) PETs. Markers in the chromosomal region 22q12.1 revealed LOH rates up to 85%. Notably, one tumor revealed a homozygous deletion in a second region at 22q12.3. LOH at this locus occurred more frequently in tumors with distant metastases (10 of 11) compared with tumors without distant metastases (3 of 12; P ¼ 0:0057) and, overall, allelic loss of 22q is positively correlated with distant metastases ðr ¼ 0:78; P , 0:0001Þ: Conclusions: These findings are suggestive for novel tumor suppressor gene loci at Chromosome 22q that might contribute to the pathogenesis of PETs, especially to the development of distant metastases.
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a novel insulinoma tumor suppressor gene locus on Chromosome 22q with potential prognostic implications
The Journal of Clinical Endocrinology and Metabolism, 2001Co-Authors: Anja Wild, P Langer, Annette Ramaswamy, Brunhilde Chaloupka, Detlef K BartschAbstract:The molecular mechanisms contributing to the tumorigenesis of insulinomas are still poorly understood. As moderate to high rates of LOH have been found on Chromosome 22q in gastrinomas, we performed a finer deletion mapping study of Chromosome 22q with 8 microsatellite markers in 15 insulinomas (4 malignant and 11 benign). Fourteen of 15 (93%) insulinomas revealed LOH on Chromosome 22q, whereas the shortest region of overlap implicated a deletion of approximately 700 kb at 22q12.1-q12.2 with an LOH rate of up to 57% (8 of 14). Although the expressed sequence tag marker A006E25 that is localized in the hSNF5/INI1 gene on 22q11.2 revealed LOH in 50% of informative cases (7 of 14), no alterations in this gene could be identified by single strand conformational polymorphism analysis, direct DNA sequencing, or RNA expression analysis. Remarkably, the four malignant tumors showed a common deleted region between markers D22S345 and D22S1144 compared with none of the 11 benign insulinomas. The observed high frequ...