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Structural Aberrations (structural + aberration)
Selected AbstractsCataracts in experimentally diabetic mouse: morphological and apoptotic changesDIABETES OBESITY & METABOLISM, Issue 2 2005K. R. Hegde Aim:, The objective of these investigations was to extend our earlier study on the induction of cataracts in diabetic mice, a low aldose reductase (AR) animal model at morphological level. Previous studies were done primarily at biochemical level. Methods:, Diabetes was induced by intraperitoneal administration of streptozotocin. The lenses isolated after the establishment of diabetes were then subjected to histologic and electron microscopic studies. Results:, Morphological alterations were characterized by shrinkage, elongation and lobulization of the nuclei of the epithelial cells. This was associated with chromatin condensation and its margination. Similar structural aberrations were also observed in a significant number of the subepithelial fibre cells representing defect in fibre maturation. More interestingly, unlike that in other common animal models of diabetic cataract, such abnormally nucleated cells were also found to be prevalent in the posterior subcapsular region, a finding common in human diabetics also. Conclusion:, The present studies further affirm the suitability of the mouse model for a study of cataractogenesis induced by diabetes. Because of the findings reported herein, as well as the known biochemical similarity between the lenses of the mice and humans in respect of AR deficiency, contrary to the rat model where it is very high, use of this species is considered more useful towards understanding the basic aetiology as well as for evaluating the efficacy of various referred nutritional and metabolic antioxidants against such cataracts. [source] Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analysesGENES, CHROMOSOMES AND CANCER, Issue 4 2010Anu Usvasalo Copy number losses in chromosome arm 9p are well-known aberrations in malignancies, including leukemias. The CDKN2A gene is suggested to play a key role in these aberrations. In this study overviewing 9p losses in hematologic neoplasias, we introduce the term focal 9p instability to indicate multiple areas of copy number loss or homozygous loss within a larger heterozygous one in 9p. We have used microarray comparative genomic hybridization to study patients with acute lymphoblastic leukemia (ALL, n = 140), acute myeloid leukemia (n = 50), chronic lymphocytic leukemia (n = 20), and myelodysplastic syndromes (n = 37). Our results show that 9p instability is restricted to ALL. In total, 58/140 (41%) patients with ALL had a loss in 9p. The 9p instability was detected in 19% of the patients with ALL and always included homozygous loss of CDKN2A along with loss of CDKN2B. Other possibly important genes included MTAP, IFN, MLLT3, JAK2, PTPLAD2, and PAX5. 13/27 (48%) patients with the instability had the BCR/ABL1 fusion gene or other oncogene-activating translocation or structural aberrations. Two patients had homozygous loss of hsa-mir ,31, a microRNA known to regulate IKZF1. IKZF1 deletion at 7p12.1 was seen in 10 (37%) patients with the 9p instability. These findings suggest that, in ALL leukemogenesis, loss of CDKN2A and other target genes in the instability region is frequently associated with BCR/ABL1 and IKZF1 dysfunction. The multiple mechanisms leading to 9p instability including physical or epigenetic loss of the target genes, loss of the microRNA cluster, and the role of FRA9G fragile site are discussed. © 2009 Wiley-Liss, Inc. [source] Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22qGENES, CHROMOSOMES AND CANCER, Issue 2 2002Krzysztof Mrózek We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for ,21 (eight of eight patients), ,5 (five of six patients), ,20 (seven of nine patients), and ,18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 21 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized. © 2002 Wiley-Liss, Inc. [source] Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell lineGENES, CHROMOSOMES AND CANCER, Issue 1 2002Kanji Kawai The tumor cell line HT-29 was derived from a primary adenocarcinoma of the rectosigmoid colon. HT-29 is hypertriploid (3n+) and has accumulated numerous chromosomal structural aberrations. To identify material involved in chromosome rearrangements, we performed a comprehensive cytogenetic analysis using G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). The combination of molecular cytogenetic techniques enabled us to define the first comprehensive karyotype for HT-29. Seventeen marker chromosomes were found in 75,100% of metaphase cells, generally in a single copy per cell. We confirmed the composition of eight previously described markers, refined the classification of seven others, and identified two novel marker chromosomes. Notable aberrations included a reciprocal translocation between chromosomes 6 and 14 and an unusual, large derivative chromosome 8 composed entirely of 8q material. The telomere status, evaluated by FISH, revealed telomeric signals at the termini of all chromosomes. No interstitial telomeric sequences were observed in any cell. Although numerous chromosomal aberrations are present in HT-29, the cell line appears to have retained a high level of genomic stability during passage in culture since undergoing transformation. The excellent resolving power of SKY, coupled with additional information obtained from molecular cytogenetic analyses, will improve our ability to identify genetic lesions characteristic of cancer. © 2002 Wiley-Liss, Inc. [source] The frequency of occurrence of abnormal frenal attachment of lips and enamel defects in Turner syndromeORAL DISEASES, Issue 2 2008A Kusiak Objective:, The aim of the work was to register the frequency of occurrence of abnormal frenal attachment of lips and enamel defects and find the correlation between these anomalies and three types of Turner syndrome. Materials and methods:, Fifty patients (aged 20,40 years) were clinically and cytogenetically diagnosed and divided into three groups, according to karyotype: 45,X (17 cases), with structural aberrations of chromosome X (12 cases) and with mosaic karyotype (21 cases). The control group consisted of 51 healthy woman aged 21,40 years. Subjects were screened for developmental anomalies in the labial frenula and enamel defects in three groups of Turner syndrome. Results:, Some significant anomalies of soft and hard tissues were found in studied patients: abnormal frenal attachments (42% of cases), enamel opacities (58% of cases) and enamel hypoplasia (38% of cases). Differences in the occurrence of these anomaly in all group with Turner syndrome in comparison with the control group were significantly different. Enamel defects were prevalent in the patients with karyotype 45,X and patients with structural aberrations of chromosome X in comparison with the mosaic karyotype. Conclusion:, The results of the present study have shown, that abnormal attachment of lips and enamel defects were more frequent in Turner syndrome patients than in the control group. Enamel defects were correlated with the karyotypes of Turner syndrome and abnormal attachment of lips was not correlated with the karyotypes of Turner syndrome. [source] Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoidesBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002X. Mao Summary Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. Objectives To investigate genetic aberrations in CTCL. Methods We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ±,SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies. [source] Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcomeCANCER SCIENCE, Issue 3 2007Panayiotis Loukopoulos We analyzed the subchromosomal numerical aberrations of 44 surgically resected pancreatic adenocarcinomas by array-based comparative genomic hybridization. The aberration profile ranged widely between cases, suggesting the presence of multiple or complementary mechanisms of evolution in pancreatic cancer, and was associated with lymph node metastasis and venous or serosal invasion. A large number of small loci, previously uncharacterized in pancreatic cancer, showed non-random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13, 14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23, 10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were amplified recurrently. We identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK, E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23 independently predicted patient outcome. Expression profiling of amplified genes identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as potential novel oncogenes. Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma. (Cancer Sci 2007; 98: 392,400) [source] | ||||||||||