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Michael Hofbeck - One of the best experts on this subject based on the ideXlab platform.
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Laterality of the aortic arch and anomalies of the subclavian artery—reliable indicators for 22q11.2 deletion syndromes?
European Journal of Pediatrics, 2004Co-Authors: Ralf Rauch, Anita Rauch, Andreas Koch, Stefan Zink, Renate Kaulitz, M Girisch, Helmut Singer, Michael HofbeckAbstract:A variety of cardiac defects, encompassing truncus arteriosus, tetralogy of Fallot, pulmonary atresia with ventricular septal defect and interrupted aortic arch, are generally summarised as conotruncal malformations. Patients with these cardiac defects were frequently found to have a common microdeletion on chromosome 22, the so-called Monosomy 22q11.2. The aim of our study was to determine whether the laterality of the aortic arch or the presence of subclavian artery anomalies (SAA) represent markers for Monosomy 22q11.2 in these patients. 170 patients with these cardiac anomalies were recruited at presentation in the paediatric cardiology units of two tertiary referral centres from 1994 until 2003. Of the 170 children and young adults, 33 had interrupted aortic arch, 35 tetralogy of Fallot, 31 truncus arteriosus communis and 71 pulmonary atresia with ventricular septal defect. All were screened for Monosomy 22q11.2 and the results were correlated with the laterality of the aortic arch and the presence of SAA contralateral to the aortic arch (aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the right subclavian artery). Monosomy 22q11.2 was present in 59/170 patients (35%). A left aortic arch (LAA) was found in 118 (69%), a right aortic arch (RAA) in 52 (31%) patients. Almost 50% of the patients with RAA (46%), but only 30% of the patients with LAA had Monosomy 22q11.2 ( P =0.054). A total of 47 patients (28%) had an anomaly of the subclavian artery, 81% of whom had Monosomy 22q11.2. This deletion was found in decreasing percentage in patients with LAA+SAA (85%) >RAA+SAA (75%) >RAA without SAA (28%) >LAA without SAA (13%). Conclusion: In patients with conotruncal malformations, anomalies of the subclavian arteries are the most important anatomical marker for the presence of Monosomy 22q11.2, independent of the laterality of the aortic arch. Therefore, we recommend cytogenetic testing for this microdeletion in all patients with subclavian artery anomalies and conotruncal malformations.
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laterality of the aortic arch and anomalies of the subclavian artery reliable indicators for 22q11 2 deletion syndromes
European Journal of Pediatrics, 2004Co-Authors: Ralf Rauch, Anita Rauch, Andreas Koch, H. Singer, Stefan Zink, Renate Kaulitz, M Girisch, Michael HofbeckAbstract:A variety of cardiac defects, encompassing truncus arteriosus, tetralogy of Fallot, pulmonary atresia with ventricular septal defect and interrupted aortic arch, are generally summarised as conotruncal malformations. Patients with these cardiac defects were frequently found to have a common microdeletion on chromosome 22, the so-called Monosomy 22q11.2. The aim of our study was to determine whether the laterality of the aortic arch or the presence of subclavian artery anomalies (SAA) represent markers for Monosomy 22q11.2 in these patients. 170 patients with these cardiac anomalies were recruited at presentation in the paediatric cardiology units of two tertiary referral centres from 1994 until 2003. Of the 170 children and young adults, 33 had interrupted aortic arch, 35 tetralogy of Fallot, 31 truncus arteriosus communis and 71 pulmonary atresia with ventricular septal defect. All were screened for Monosomy 22q11.2 and the results were correlated with the laterality of the aortic arch and the presence of SAA contralateral to the aortic arch (aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the right subclavian artery). Monosomy 22q11.2 was present in 59/170 patients (35%). A left aortic arch (LAA) was found in 118 (69%), a right aortic arch (RAA) in 52 (31%) patients. Almost 50% of the patients with RAA (46%), but only 30% of the patients with LAA had Monosomy 22q11.2 (P=0.054). A total of 47 patients (28%) had an anomaly of the subclavian artery, 81% of whom had Monosomy 22q11.2. This deletion was found in decreasing percentage in patients with LAA+SAA (85%) >RAA+SAA (75%) >RAA without SAA (28%) >LAA without SAA (13%). Conclusion:In patients with conotruncal malformations, anomalies of the subclavian arteries are the most important anatomical marker for the presence of Monosomy 22q11.2, independent of the laterality of the aortic arch. Therefore, we recommend cytogenetic testing for this microdeletion in all patients with subclavian artery anomalies and conotruncal malformations.
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Cervical origin of the subclavian artery as a specific marker for Monosomy 22q11.
American Journal of Cardiology, 2002Co-Authors: R. Rauch, Anita Rauch, Andreas Koch, Matthias Kumpf, Andreas Dufke, H. Singer, Michael HofbeckAbstract:In our study of 136 patients with conotruncal malformations, anomalies of the subclavian arteries were present in >60% of children with Monosomy 22q11. Because cervical origin of the right subclavian artery was exclusively found in patients with Monosomy 22q11, this anomaly might represent a specific marker for this microdeletion.
Arun D Singh - One of the best experts on this subject based on the ideXlab platform.
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Monosomy 3 by fish in uveal melanoma variability in techniques and results
Survey of Ophthalmology, 2012Co-Authors: Mary E Aronow, Ray Tubbs, Yogen Saunthararajah, Charles V Biscotti, Pierre L Triozzi, Arun D SinghAbstract:Abstract Tumor Monosomy 3 confers a poor prognosis in patients with uveal melanoma. We critically review the techniques used for fluorescence in situ hybridization (FISH) detection of Monosomy 3 in order to assess variability in practice patterns and to explain differences in results. Significant variability that has likely affected reported results was found in tissue sampling methods, selection of FISH probes, number of cells counted, and the cut-off point used to determine Monosomy 3 status. Clinical parameters and specific techniques employed to report FISH results should be specified so as to allow meta-analysis of published studies. FISH-based detection of Monosomy 3 in uveal melanoma has not been performed in a standardized manner, which limits conclusions regarding its clinical utility. FISH is a widely available, versatile technology, and when performed optimally has the potential to be a valuable tool for determining the prognosis of uveal melanoma.
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variation of Monosomy 3 status within uveal melanoma
Archives of Pathology & Laboratory Medicine, 2009Co-Authors: Lynn Schoenfield, James Pettay, Ray Tubbs, Arun D SinghAbstract:CONTEXT: Determining the most significant prognostic variables in uveal melanoma is important for stratifying patients for metastasis surveillance and possible initiation of chemotherapy or immunotherapy. Monosomy 3, one such variable, can be determined using fluorescence in situ hybridization, either on enucleated samples, fine-needle aspiration biopsy, or tumor sample obtained by vitrector. OBJECTIVE: To evaluate possible regional discordance in chromosome 3 by sites likely to be sampled by different biopsy methods. DESIGN: Eighteen consecutive patients with uveal melanoma who underwent primary enucleation were studied. Representative paraffin blocks were selected based on review of hematoxylin-eosin stained sections, and the apex and base of each tumor was demarcated. Unstained paraffin sections, 4 mum in thickness, were prepared, and fluorescence in situ hybridization, looking for Monosomy 3, was performed. The chromosomal analysis was also correlated with histologic evaluation for melanoma cell type (spindle vs epithelioid cell), ciliary body involvement, presence of positive periodic acid-Schiff vascular mimicry patterns, scleral or extrascleral spread and size. One case was excluded because of necrosis. RESULTS: Ten of the 17 remaining cases (59%) demonstrated Monosomy 3 (in either the base or both base and apex of the tumor) with 7 cases (41%) showing disomy. Seven cases (70%) with Monosomy 3 demonstrated this in both the apex and the base locations, whereas 3 cases (30%) showed Monosomy in one location only (always at the base). Fourteen of the 17 cases (82%) revealed concordance in chromosome 3-Monosomy 3 (7 of 14, 50%) or chromosome 3-disomy 3 (7 of 14, 50%). All 3 discordant cases demonstrated the Monosomy 3 at the base with disomy at the apex. Lack of concordance between the base and apex did not correlate with melanoma cell type. CONCLUSIONS: Prognostic variables are important in management of neoplasms, and this study points out that the site of tissue biopsy for prognostication in uveal melanoma could affect the results obtained, at least for the presence of Monosomy 3.
Martine J Jager - One of the best experts on this subject based on the ideXlab platform.
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effect of heterogeneous distribution of Monosomy 3 on prognosis in uveal melanoma
Archives of Pathology & Laboratory Medicine, 2011Co-Authors: Inge H G Bronkhorst, Willem Maat, Ekaterina S Jordanova, Wilma G M Kroes, Nicoline E Schalijdelfos, Gregorius P M Luyten, Martine J JagerAbstract:Context.—Fluorescence in situ hybridization (FISH) analyses on tumor sections and on isolated nuclei showed that even low numbers of cells with Monosomy of chromosome 3 adversely affected survival. Objective.—To determine what percentage of uveal melanoma cells with Monosomy of chromosome 3 influences patient mortality. Design.—To determine the presence of Monosomy 3, karyotyping and FISH on cultured cells and FISH on isolated nuclei were performed on 50 primary uveal melanomas. Clinical and pathologic prognostic factors were assessed and compared with 5-year survival data. Analyses were performed using Cox proportional hazards test, log-rank analysis, sensitivity, specificity, and positive and negative likelihood ratios. Results.—Combined karyotyping and FISH on cultured cells showed Monosomy 3 in 19 of 50 cases (38%), whereas determination of the Monosomy 3 status by FISH on isolated nuclei with a threshold of 5% assigned 31 of 50 cases (62%) to the Monosomy-3 category. When Monosomy 3 on isolated nucle...
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the heterogeneous distribution of Monosomy 3 in uveal melanomas implications for prognostication based on fine needle aspiration biopsies
Archives of Pathology & Laboratory Medicine, 2009Co-Authors: Willem Maat, Ekaterina S Jordanova, Nicoline E Schalijdelfos, Shama L Van Zelderenbhola, Ed R Barthen, Hans W Wessels, Martine J JagerAbstract:Abstract Context.—The detection of Monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect Monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor. Objective.—To study the distribution of Monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH). Design.—We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with Monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue. Results.—Combining karyotyping and FISH on cultured cells identified Monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffi...
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Monosomy of chromosome 3 and an inflammatory phenotype occur together in uveal melanoma
Investigative Ophthalmology & Visual Science, 2008Co-Authors: Willem Maat, Ekaterina S Jordanova, Nicoline E Schalijdelfos, Long V Ly, Didi De Wolffrouendaal, Martine J JagerAbstract:PURPOSE. In uveal melanoma, different predictors of poor prognosis have been identified, including Monosomy of chromosome 3, HLA expression, and the presence of infiltrating leukocytes and macrophages. Each of these parameters can be used to differentiate prognostically the favorable tumors from the unfavorable ones, and thus the hypothesis for the present study was that they are related, and that Monosomy of chromosome 3 occurs in the same tumors as the unfavorable inflammatory phenotype. METHODS. Tumor tissue was obtained from 50 cases of uveal melanoma treated between 1999 and 2004. After enucleation, nuclei were isolated from paraffin-embedded tissue for fluorescence in situ hybridization, to determine the chromosome 3 copy number. Each tumor-containing globe was further processed for conventional histopathologic examination and for immunohistochemical analysis with HLA class I and II‐specific antibodies and with macrophage marker CD68. RESULTS. Of 50 uveal melanomas, 62% (31/50) were categorized as having Monosomy of chromosome 3. Monosomy 3 was associated with the presence of epithelioid cells, an increased density of tumor-infiltrating macrophages, and a higher HLA class I and II expression. Survival analyses showed a correlation between Monosomy 3 and decreased survival and identified Monosomy 3, ciliary body involvement, and largest basal tumor diameter as the best prognostic markers. CONCLUSIONS. Monosomy 3 in uveal melanoma is associated with the presence of an inflammatory phenotype, consisting of a high HLA class I and II expression as well as an increased number of tumor-infiltrating macrophages. In a multivariate Cox regression analysis, the presence of Monosomy 3 was one of the best prognostic markers of metastatic disease and survival, although the follow-up time was short. (Invest Ophthalmol Vis Sci. 2008;49:505‐510) DOI:10.1167/ iovs.07-0786
Jerry A Shields - One of the best experts on this subject based on the ideXlab platform.
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Small choroidal melanoma with Monosomy 3.
Middle East African Journal of Ophthalmology, 2010Co-Authors: Fariba Ghassemi, Carol L Shields, Miguel A Materin, Jerry A ShieldsAbstract:PURPOSE: To report a patient with small juxtapapillary choroidal melanoma with chromosome 3 Monosomy treated with I(125) plaque and transpupillary thermotherapy (TTT). A 64-year-old Caucasian male presented with painless blurred vision of the left eye. Ocular examination disclosed a small juxtapapillary choroidal melanocytic tumor with overlying subretinal fluid and orange pigment. Ultrasound showed an elevated choroidal mass of 2 mm thickness with low reflectivity on A-scan and hollowness on B scan, consistent with a small choroidal melanoma. The patient was treated with plaque I(125) radiotherapy combined with one session of TTT. Genetic testing of the tumor cells obtained by fine needle aspiration biopsy showed chromosome 3 Monosomy. At 1 year after treatment, the tumor was regressed with resolution of subretinal fluid and 20/40 visual acuity. A small choroidal melanoma can manifest Monosomy of chromosome 3, a known predictive factor for the development of systemic metastasis.
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small choroidal melanoma with chromosome 3 Monosomy on fine needle aspiration biopsy
Ophthalmology, 2007Co-Authors: Carol L Shields, Miguel A Materin, Luiz Teixeira, Arman Mashayekhi, Arupa Ganguly, Jerry A ShieldsAbstract:Purpose To evaluate the presence of chromosome 3 Monosomy in small choroidal melanoma using fine-needle aspiration biopsy (FNAB). Design Noncomparative case series. Participants Fifty-six patients with small choroidal melanoma measuring 3 mm or less in thickness who were undergoing plaque radiotherapy. Methods Fine-needle aspiration biopsy was used at the time of plaque radiotherapy to sample tumor cells using a 27-gauge long needle via an indirect transvitreal approach into the tumor apex for postequatorial tumors or a 30-gauge short needle via a direct transscleral approach into the tumor base for preequatorial tumors. Main Outcome Measures Chromosome 3 Monosomy in small choroidal melanoma. Results The median tumor thickness was 2.6 mm. Monosomy 3 was found in 15 (27%) cases and disomy 3 was found in 32 (57%) cases. In 9 (16%) cases, genomic DNA yield was insufficient for genetic analysis. Fine-needle aspiration biopsy with a 27-gauge needle transvitreal approach provided quantity sufficient for genetic testing in 31 (97%) of 32 cases versus 16 (67%) of 24 cases sampled with a 30-gauge transscleral technique. Compared with disomy 3 tumors, Monosomy 3 tumors were statistically more likely to occur in older patients ( P = 0.040). Monosomy 3 (versus disomy 3) tumors showed thickness of more than 2 mm in 100% (vs. 84%), subretinal fluid in 87% (vs. 94%), symptoms in 40% (vs. 56%), orange pigment in 93% (vs. 81%), and margin of 3 mm or less to the optic disc in 20% (vs. 50%). There was no statistical difference between Monosomy 3 and disomy 3 tumors in the presence or number of these clinical factors. However, small choroidal melanomas with Monosomy 3 mutation were more likely to have had documented growth (63%) compared with those with disomy 3 (25%; P = 0.025; odds ratio, 5.00). Conclusions Using FNAB at the time of plaque radiotherapy, Monosomy 3 was found in approximately 27% of small choroidal melanomas, more often in older patients and tumors with documented growth. Transvitreal biopsy into the tumor apex provided better yield compared with transscleral biopsy into the tumor base.
Robert F. Hevner - One of the best experts on this subject based on the ideXlab platform.
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Neuropathology of brain and spinal malformations in a case of Monosomy 1p36 - eScholarship
2020Co-Authors: Lisa G Shaffer, Anthony Barkovich, Naoko Shiba, Ram Daza, William B. Dobyns, Robert F. HevnerAbstract:Monosomy 1p36 is the most common subtelomeric chromosomal deletion linked to mental retardation and seizures. Neuroimaging studies suggest that Monosomy 1p36 is associated with brain malformations including polymicrogyria and nodular heterotopia, but the h
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neuropathology of brain and spinal malformations in a case of Monosomy 1p36
Acta neuropathologica communications, 2013Co-Authors: Naoko Shiba, Lisa G Shaffer, Ram Daza, William B. Dobyns, Robert F. Hevner, James A BarkovichAbstract:Monosomy 1p36 is the most common subtelomeric chromosomal deletion linked to mental retardation and seizures. Neuroimaging studies suggest that Monosomy 1p36 is associated with brain malformations including polymicrogyria and nodular heterotopia, but the histopathology of these lesions is unknown. Here we present postmortem neuropathological findings from a 10 year-old girl with Monosomy 1p36, who died of respiratory complications. The findings included micrencephaly, periventricular nodular heterotopia in occipitotemporal lobes, cortical dysgenesis resembling polymicrogyria in dorsolateral frontal lobes, hippocampal malrotation, callosal hypoplasia, superiorly rotated cerebellum with small vermis, and lumbosacral hydromyelia. The abnormal cortex exhibited “festooned” (undulating) supragranular layers, but no significant fusion of the molecular layer. Deletion mapping demonstrated single copy loss of a contiguous 1p36 terminal region encompassing many important neurodevelopmental genes, among them four HES genes implicated in regulating neural stem cell differentiation, and TP73, a monoallelically expressed gene. Our results suggest that brain and spinal malformations in Monosomy 1p36 may be more extensive than previously recognized, and may depend on the parental origin of deleted genes. More broadly, our results suggest that specific genetic disorders may cause distinct forms of cortical dysgenesis.
