Use of fluorescence in situ hybridization to detect loss of chromosome 10 in astrocytomas

1995 ◽  
Vol 83 (2) ◽  
pp. 316-323 ◽  
Author(s):  
Stephen J. Dalrymple ◽  
John F. Herath ◽  
Steven R. Ritland ◽  
Cheryl A. Moertel ◽  
Robert B. Jenkins
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Fish Analysis ◽  
Chromosome 10 ◽  
Content Type ◽  
Valuable Adjunct ◽  
Length Polymorphisms ◽  
Grade Ii ◽  
Fine Print

✓ Models describing progression in the genetic derangement of glial tumors have shown loss of chromosome 10 to occur most frequently in high-grade lesions, suggesting that identification of this loss may be prognostically significant. Fluorescence in situ hybridization (FISH) analysis may be a valuable adjunct to histological grading if it can accurately detect this loss. In this paper the authors correlate results obtained from FISH, cytogenetic, molecular genetic, and flow cytometric analyses of a series of 39 brain specimens, including seven normal, two gliotic, and 30 neoplastic (one Grade II, one Grade III, and 28 Grade IV astrocytoma) specimens. Contiguous section of freshly resected surgical tissue were submitted for tissue culturing (karyotype) and touch preparation (FISH), snap-frozen (molecular genetic), or paraffin-embedded (histology and flow cytometry). Centromere-specific probes for chromosomes 10 and 12 were used for FISH analysis, and 19 restriction fragment length polymorphisms (two p-arm and 17 q-arm) and four microsatellite sequence polymorphisms (three p-arm and one q-arm) were used for molecular genetic analysis of chromosome 10. Findings showed FISH and loss of heterozygosity (LOH) analyses to be concordant in 33 of 38 specimens (sensitivity 94%, specificity 81%), with one specimen indeterminate on LOH analysis. Both FISH and LOH analyses were more sensitive at detecting chromosome 10 loss than conventional cytogenetic (karyotype) analysis. The authors conclude that FISH is a sensitive test for detecting chromosome 10 loss and ploidy in astrocytic tumors.

Central neurocytoma: morphological, flow cytometric, polymerase chain reaction, fluorescence in situ hybridization, and karyotypic analyses

1999 ◽  
Vol 90 (2) ◽  
pp. 348-354 ◽  
Author(s):  
Venita Jay ◽  
Vern Edwards ◽  
Eelco Hoving ◽  
James Rutka ◽  
Laurence Becker ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
In Situ Hybridization ◽  
Ganglion Cells ◽  
Molecular Genetic ◽  
Central Neurocytoma ◽  
Molecular Genetic Analysis ◽  
Fish Analysis ◽  
Chain Reaction ◽  
Polymerase Chain

✓ The results of cytogenetic and molecular genetic analysis of a central neurocytoma are presented. Central neurocytomas are intriguing neoplasms that exhibit primarily neuronal, but also glial characteristics, which indicate an origin from a pluripotential neuroglial precursor. The authors describe an intraventricular neurocytoma in an 11-year-old boy that showed anaplastic features with widespread necrosis and mitoses, as well as extensive calcification and foci that exhibited marked neuronal differentiation with clusters of ganglion cells. Immunohistochemical examination showed prominent synaptophysin and neurofilament positivity and focal glial fibrillary acidic protein positivity. Electron microscopy revealed abundant neuritic processes with microtubules and dense core granules as well as mature ganglion cells. Flow cytometry studies revealed increased S (7.8%) and G2M (9.7%) phase components. Molecular and cytogenetic studies were undertaken to assess whether there were similarities to two other tumor types that exhibit neuronal differentiation, the neuroblastoma and medulloblastoma. Polymerase chain reaction and fluorescence in situ hybridization (FISH) analysis revealed no evidence of amplification of the MYCN oncogene or chromosome 1p deletion, which are common in neuroblastomas. Chromosomal analysis by G banding revealed a complex karyotype, with counts in the near-diploidy range (45–48). Two chromosomes 1 appeared normal on G banding and FISH analysis, with p58 signals present on the distal p arm of both chromosomes 1; however, three additional copies of distal 1q were present in rearrangements with 4 and 7. Although the histological findings indicate a kinship to the neuroblastoma and medulloblastoma, the central neurocytoma appears to have a different karyotypic profile, although more cases need to be assessed using molecular genetic analysis.

Focal hyperperfusion in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes

2001 ◽  
Vol 94 (1) ◽  
pp. 133-136 ◽  
Author(s):  
Kenichi Amagasaki ◽  
Tsuneo Shimizu ◽  
Yoko Suzuki ◽  
Toshiyuki Kakizawa
Keyword(s):  
Lactic Acidosis ◽  
Genetic Analysis ◽  
Mitochondrial Myopathy ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Metabolic Dysfunction ◽  
Nucleotide Pair ◽  
Content Type ◽  
Typical Point ◽  
Fine Print

✓ 28-year-old woman presented with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The diagnosis was based on the results of molecular genetic analysis, which indicated a typical point mutation at the nucleotide pair 3243. Xenon computerized tomography scans obtained during the strokelike episodes revealed the lesion responsible for the symptoms to be an area of focal hyperperfusion, and scans obtained after the episodes revealed an area of hypoperfusion. Pathogenesis of the strokelike episodes appears to be metabolic dysfunction, although the involvement of a vascular event cannot be excluded.

Diffuse leptomeningeal involvement by a ganglioglioma in a child

1992 ◽  
Vol 77 (2) ◽  
pp. 302-306 ◽  
Author(s):  
Margaret R. Wacker ◽  
Philip H. Cogen ◽  
Joan E. Etzell ◽  
Laleh Daneshvar ◽  
Richard L. Davis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Sequences ◽  
Tumor Tissue ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Content Type ◽  
Leptomeningeal Involvement ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Fine Print

✓ Gangliogliomas are tumors composed of neuronal and glial elements that typically grow slowly by expansion only. This report describes a 20-month-old girl with a ganglioglioma that extensively involved the subarachnoid space; microscopic foci of tumor were found in the brain and spinal cord. Despite chemotherapy and radiation therapy, the child died 5 months after diagnosis. Molecular genetic analysis showed loss of chromosome 17p DNA sequences in the tumor tissue.

Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study

1998 ◽  
Vol 88 (6) ◽  
pp. 1111-1115 ◽  
Author(s):  
Kalman Kovacs ◽  
Eva Horvath ◽  
Lucia Stefaneanu ◽  
Juan Bilbao ◽  
William Singer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
In Situ Hybridization ◽  
Pituitary Adenoma ◽  
Immunoelectron Microscopy ◽  
Secretory Granules ◽  
Cell Types ◽  
Content Type ◽  
Separate Cell ◽  
Fine Print

✓ The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH. The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells—one somatotroph and one corticotroph—transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.

Chromosome Banding in Amphibia. XXXV. Highly Mobile Nucleolus Organizing Regions in Craugastor fitzingeri (Anura, Craugastoridae)

2017 ◽  
Vol 152 (4) ◽  
pp. 180-193 ◽  
Author(s):  
Michael Schmid ◽  
Claus Steinlein ◽  
Wolfgang Feichtinger ◽  
Indrajit Nanda
Keyword(s):  
Chromosome Banding ◽  
Cytogenetic Study ◽  
Variable Number ◽  
28S Rdna ◽  
Fish Analysis ◽  
Intraindividual Variation ◽  
Length Polymorphisms ◽  
Somatic Tissues

A 7-year cytogenetic study on the leaf litter frog Craugastor fitzingeri from Costa Rica and Panama revealed the existence of highly mobile nucleolus organizing regions (NORs) in their genomes. Silver (Ag)-staining of the active NORs demonstrated an exceptional interindividual pattern of NOR distribution at the telomeres of the chromosomes. All individuals examined showed a different and specific NOR location in their karyotypes. Furthermore, intraindividual variation in the NOR sites was found. This observation suggested the existence of mobile NORs in C. fitzingeri. Confirmation of this phenomenon was possible by systematic FISH analysis using an 18S + 28S rDNA probe. The extremely variable number and position of the NORs in C. fitzingeri is best explained by highly mobile NORs that move freely between the telomeres of the chromosomes. These transpositions must occur preferentially in premeiotic, meiotic, or postmeiotic stages, but also at a lower incidence in the somatic tissues of the animals. It is hypothesized that transposable (mobile) elements are closely linked to the NORs or are inserted into the major 18S + 28S rDNA spacers of C. fitzingeri. When such transposable elements spread by transpositions, they can carry with them complete or partial NORs. The present study provides detailed information on various differential chromosome banding techniques, in situ hybridization experiments, chromosomal hypermethylation patterns, determination of the genome size, and analyses of restriction fragment length polymorphisms of the DNA.

Analysis of loss of heterozygosity on chromosomes 10q, 11, and 16 in medulloblastomas

2001 ◽  
Vol 94 (5) ◽  
pp. 799-805 ◽  
Author(s):  
Xiao-lu Yin ◽  
Jesse C. Pang ◽  
Yan-hui Liu ◽  
Edith Y. Chong ◽  
Yue Cheng ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Molecular Genetic ◽  
Genetic Material ◽  
Suppressor Genes ◽  
Blood Samples ◽  
Content Type ◽  
Targeted Deletion ◽  
Fine Print

Object. The loss of genetic material from specific chromosome loci is a common feature in the oncogenesis of tumors and is often indicative of the presence of important tumor suppressor genes at these loci. Recent molecular genetic analyses have demonstrated frequent loss of chromosomes 10q, 11, and 16 in medulloblastomas. The aim of this study was to localize the targeted deletion regions on the three aforementioned chromosomes in medulloblastomas. Methods. Loss of heterozygosity (LOH) was examined on chromosomes 10q, 11, and 16 in a series of 22 primary and two recurrent medulloblastomas by using polymerase chain reaction—based microsatellite analysis. The DNA extracted from the tumors and corresponding normal blood samples were amplified independently in the presence of radioactively labeled microsatellite primers, resolved by denaturing gel electrophoresis and processed for autoradiography. The DNA obtained from control blood samples that displayed allelic heterozygosity at a given microsatellite locus were considered informative. Loss of heterozygosity was inferred when the allelic signal intensity of the tumor sample was reduced by at least 40%, relative to that of the constitutional control. The LOH analysis demonstrated that deletions of chromosomes 10q, 11p, and 16q are recurrent genetic events in the development of medulloblastomas. Three subchromosomal regions of loss have been identified and are localized to the deleted in malignant brain tumors 1 [DMBT1] gene site on chromosomes 10q25, 11p13–11p15.1, and 16q24.1–24.3. Conclusions. These results indicate that DMBT1 is closely associated with the oncogenesis of medulloblastomas and highlight regions of loss on chromosomes 11p and 16q for further fine mapping and cloning of candidate tumor suppressor genes that are important for the genesis of medulloblastoma.

Analysis of loss of heterozygosity for chromosome 10 in patients with malignant astrocytic tumors: correlation with patient age and survival

2001 ◽  
Vol 95 (4) ◽  
pp. 651-659 ◽  
Author(s):  
Kenji Tada ◽  
Shoji Shiraishi ◽  
Takanori Kamiryo ◽  
Hideo Nakamura ◽  
Hirofumi Hirano ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Chromosome 10 ◽  
Patient Age ◽  
Content Type ◽  
Unfavorable Prognostic Factor ◽  
Patient Âgé ◽  
Fine Print

Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Anatomical data on the craniocervical junction and their correlation with degenerative changes in 30 cadaveric specimens

2005 ◽  
Vol 3 (5) ◽  
pp. 379-385 ◽  
Author(s):  
Stefan A. König ◽  
Axel Goldammer ◽  
Hans-Ekkehart Vitzthum
Keyword(s):  
Articular Cartilage ◽  
Articular Surface ◽  
Craniocervical Junction ◽  
Degenerative Changes ◽  
Content Type ◽  
Articular Surfaces ◽  
Anatomical Data ◽  
Grade Ii ◽  
Grade Iii ◽  
Fine Print

>Object. The goal of this project was to measure vertebral dimensions at the craniocervical junction and to investigate degenerative changes in this region and their correlations with the anatomical data. These studies will assist in an understanding of biomechanical conditions in this region, which are clinically relevant in cases of cervicogenic headaches and vertigo. Methods. The authors examined 30 cadaveric specimens obtained from patients ranging in age from 24 to 88 years at death. Measurements of angles of the vertebrae were conducted using an imprint method. Microsections of osseous endplates and articular cartilage were graded according to their degrees of degeneration by using the Petersson classification (0, no sign of degeneration; I, superficial degeneration with several fragmentations; II, deeper degeneration with cartilaginous disintegration and penetrating ulceration; or III, complete cartilaginous degeneration with the appearance of subchondral bone in > 50% of the articular surface). The authors found Grade I changes in 100% of the occiput specimens. In the superior articular cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I changes, 14% Grade II, and 20% Grade III changes. In the superior articular cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade II changes. At the occiput—C1 level the authors found a higher frequency of degeneration at the upper left articular surface of the atlas (Quadrants 1 and 3), and at the C1–2 level they found a higher frequency of degeneration at the upper left and upper right articular surfaces of the axis (Quadrants 2 and 3, respectively). Using the McNemar test, the authors investigated the frequency of affection of single quadrants in a left—right side comparison (lateral reversal). Significant differences were identified for Quadrant 2 of the upper left articular surface of C-2 and Quadrant 3 of the upper right articular surface of C-2. These results correlate with the analysis of single articular surfaces of the axis, but contradict the results for the atlas, in which no significant difference in the left—right side comparison was found. Conclusions. Severe degeneration in the atlantooccipital joints appears to be a rare condition, with no Grade II or III degeneration found in the occipital condyles and 6% Grade I, 89% Grade II, but no Grade III changes in the superior articular cartilage of the atlas. Degeneration of the inferior articular cartilage of C-1 and the superior articular cartilage of C-2 indicates that the atlantoaxial joint faces more intense mechanical exposure, which is increased at the upper joint surfaces.

The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2719-2721 ◽  
Author(s):  
Yoshitaka Hosokawa ◽  
Yumiko Maeda ◽  
Ryo Ichinohasama ◽  
Ikuo Miura ◽  
Masafumi Taniwaki ◽  
...  
Keyword(s):  
B Cell ◽  
Molecular Genetic ◽  
Regulatory Region ◽  
B Cell Lymphoma ◽  
Molecular Genetic Analysis ◽  
B Cell Differentiation ◽  
Polymerase Chain ◽  
Large B Cell

The BCL6 gene, isolated from the breakpoints of 3q27-associated chromosomal translocations, has been implicated in diffuse large B-cell lymphomas (DLBL). Here we describe the molecular characterization of novel t(3;7)(q27;p12) translocations in 2 patients with DLBL. Molecular genetic analysis of the breakpoint area involving BCL6 revealed the presence of the Ikaros gene, a central regulator of lymphoid differentiation that had been mapped to human chromosome 7 band p13-p11.1. As a molecular consequence of the translocation, the 5′ regulatory region of the BCL6 gene was replaced by the putative 5′ regulatory region of theIkaros gene, probably leading to deregulated expression of theBCL6 gene throughout B-cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) analyses of a patient sample established that the t(3;7)(q27;p12) results in fusion of the Ikaros andBCL6 genes. This study provides the first evidence that the Ikaros gene is rearranged in human hematopoietic malignant disorders.

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