13 results on '"Interphase-fish"'
Search Results
2. Chronic lymphocytic leukemia with del13q14 as the sole abnormality: dynamic prognostic estimate by interphase-FISH.
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Orlandi, Ester M., Bernasconi, Paolo, Pascutto, Cristiana, Giardini, Ilaria, Cavigliano, Paola M., Boni, Marina, Zibellini, Silvia, and Cazzola, Mario
- Abstract
This study analyzed 140 patients with isolated del13q14 on interphase FISH (I-FISH), to identify subsets with a different progression risk and to assess the acquisition of additional chromosomal abnormalities (clonal evolution) in treatment-naïve del13q14 patients. A monoallelic deletion (del13qx1) was detected in 123 cases (88%), a biallelic deletion (del13qx2) in eight and a mosaic of monoallelic and biallelic deletions (del13qx1/del13qx2) in nine. In 33% of cases, deletion encompassed the Rb1 locus The median percentage of abnormal nuclei was 50% (15%-96%), and it was higher in patients with a biallelic/mosaic pattern in comparison with patients with monoallelic deletion. Sixty two patients (44%) have been treated; 5-year treatment free survival rate was 56% and the median treatment free survival was 65 months. The baseline percentage of deleted nuclei, as a continuous variable, was related to progression (HR: 1.02; p = 0.001). According to deletion burden, three groups were identified: 64 cases (46%) had <50% deleted nuclei, 47 (33%) had 50-69% deleted nuclei, and 29 (21%) had ≥70% deleted nuclei. The 5-year untreated rate was 70.5% , 52.6% and 28.7% ( p < 0.0001), respectively. In multivariate analysis using IGHV mutational status, presence of a nullisomic clone, CD38 expression and percentage of deleted nuclei as covariates, only IGHV mutational status and the percentage of deleted nuclei were independent risk factors for treatment. In 103 patients serially monitored by I-FISH before starting any treatment, we observed a significant increase in the proportion of del13q14 cells, and this increase affected the risk of subsequent treatment requirement (HR 2.54, p = 0.001). The appearance of a new clone was detected in 16 patients (15.5%) and chromosome 13 was involved in 14 of them. I-FISH monitoring proves worthwhile for a dynamic risk stratification and for planning clinical surveillance. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2013
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3. Molecular cytogenetic evaluation of the efficacy of photodynamic therapy by indocyanine green in breast adenocarcinoma MCF-7 cells.
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Abo-Zeid, Mona A.M., Liehr, Thomas, El-Daly, Sherien M., Gamal-Eldeen, Amira M., Glei, Michael, Shabaka, Ali, Bhatt, Samarth, and Hamid, Ahmed
- Abstract
Summary: Background: Photodynamic therapy (PDT) is used for the treatment of many types of predominantly epithelial cancers. Photosensitizer is taken up by fast growing tumor cells more actively than by other body cells and is activated by light, generating reactive oxygen species that cause cell death by necrosis or apoptosis. This study aimed to evaluate the efficacy of PDT with indocyanine green (ICG) through the investigation of TP53, HER-2 and TOP2A genes signals as breast cancer gene markers by interphase fluorescence in situ hybridization (nuc-FISH). Methods: The photosynthetizer ICG (200μM) was applied to breast cancer cell line MCF-7 cells (adenocarcinoma) in combination with laser irradiation (807nm) exposure for 20min and then incubated for 12, 24 and 48h. Cell viability was evaluated using trypan blue. The signals for nuc-FISH was investigated and counted for probes specific for the genes TP53 (17p13), HER-2 (17q11.2-q12), and TOP2A (17q21-q22), and BAC-probes RP11-746M1 in 17p11.2 and RP11-403E9 in 17q11.2. Results: The cell viability of MCF-7 did not reduced significantly when the cells were treated with ICG (200μM) or exposed to laser irradiation for 20min followed by incubation for 24h. ICG/PDT treatment with laser irradiation exposure for 20min reduced the cell viability after incubating cells for 12, 24 and 48h highly significantly in a time dependent manner. For nuc-FISH analysis, TP53, HER-2, TOP2A, RP11-746M1 and RP11-403E9 signals did not reduce or increase in a significant manner when the cells were treated with ICG or exposed to laser irradiation for 20min then incubated for 24h. PDT enhanced amplification of TP53 signals from nuc ish 17p13(TP53×2) to nuc ish 17p13(TP53×3) or nuc ish 17p13(TP53×4). However, the signals of HER-2 gene, TOP2A gene and BAC probes were reduced highly significantly when MCF-7 cells were treated with PDT with all time intervals. Conclusion: ICG/PDT and laser induced cytotoxic effect in MCF-7 cells. Also, PDT enhanced TP53 gene amplification, and reduced HER-2, TOP2A, and BAC probes RP11-746M1 and RP11-403E9 signals. Therefore ICG/PDT can be used for breast cancer treatment. It has the potential to induce apoptotic effect and reduce HER-2 and TOP2A genes propagation. Further in vivo studies are needed to evaluate ICG/PDT as a promising therapeutic approach for breast cancer. [Copyright &y& Elsevier]
- Published
- 2013
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4. Glioblastomas with oligodendroglial component-common origin of the different histological parts and genetic subclassification.
- Author
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Klink, Barbara, Schlingelhof, Ben, Klink, Martin, Stout-Weider, Karen, Patt, Stephan, and Schrock, Evelin
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OLIGODENDROGLIA , *GENETICS , *HISTOLOGY , *ONCOLOGY ,BRAIN tumor genetics - Abstract
Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data. Methods: The oligodendroglial and the 'classic' glioblastoma parts of 13 GBMO were analyzed separately by interphase fluoreszence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue. Results: We identified four distinct genetic subtypes in 13 GBMOs: an 'astrocytic' subtype (9/13) characterized by +7/-10; an 'oligodendroglial' subtype with -1p/-19q (1/13); an 'intermediate' subtype showing +7/-1p (1/13), and an 'other' subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part. Conclusion: Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients. [ABSTRACT FROM AUTHOR]
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- 2011
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5. Glioblastomas with oligodendroglial component - common origin of the different histological parts and genetic subclassification.
- Author
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Klink, Barbara, Schlingelhof, Ben, Klink, Martin, Stout-Weider, Karen, Patt, Stephan, and Schrock, Evelin
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OLIGODENDROGLIA , *BRAIN tumors , *GENETICS , *ASTROCYTOMAS , *FLUORESCENCE in situ hybridization , *COMPARATIVE genomic hybridization - Abstract
Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data. Methods: The oligodendroglial and the 'classic' glioblastoma parts of 13 GBMO were analyzed separately by interphase fluorescence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue. Results: We identified four distinct genetic subtypes in 13 GBMOs: an 'astrocytic' subtype (9/13) characterized by +7/-10; an 'oligodendroglial' subtype with -1p/-19q (1/13); an 'intermediate' subtype showing +7/-1p (1/13), and an 'other' subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part. Conclusion: Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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6. Interphase-FISH study in three patients with tetraploid/diploid mosaicism
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Cavalcanti, Denise P. and Zanchetta, Luciene M.
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MOSAICISM , *CHROMOSOME abnormalities , *FIBROBLASTS , *FAILURE to thrive syndrome - Abstract
Abstract: We report tetraploid/diploid mosaicism in a boy and two girls detected by cultured skin fibroblasts. In all these children, interphase-FISH using DXZ1 probe confirmed the original karyotype. Tetraploid mosaicism was also confirmed by α-satellite probes from chromosomes 2, 6, 7, 9, 10, 17, 18 and Y in fibroblasts from the boy. The common features in these children are failure to thrive, slight mental deficiency and some degree of body asymmetry. The advantage of using interphase-FISH is the possibility of analysing a great number of cells in short time, thus giving a more precise percentage with regard to abnormal cells. [Copyright &y& Elsevier]
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- 2005
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7. Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding.
- Author
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Nordgren, Ann, Heyman, Mats, Sahlén, Sigrid, Schoumans, Jacqueline, Söderhäll, Stefan, Nordenskjöld, Magnus, and Blennow, Elisabeth
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CHROMOSOME abnormalities , *LYMPHOBLASTIC leukemia in children , *FLUORESCENCE in situ hybridization - Abstract
Abstract: Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7–15 copies) of AML1 . Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL. [ABSTRACT FROM AUTHOR]
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- 2002
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8. Favourable outcome of de novo advanced phases of childhood chronic myeloid leukaemia
- Author
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Meinolf Suttorp, Natacha Maledon, Frédéric Millot, Joelle Guilhot, Adalet Meral Güneş, Krzysztof Kałwak, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri/Çocuk Sağlığı Ve Hastalıkları Bölümü., Güneş, Adalet Meral, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pediatric Hematology and Oncology (MHH), and Hannover Medical School [Hannover] (MHH)
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0301 basic medicine ,Male ,Cancer Research ,Time Factors ,Survival ,Databases, Factual ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Childhood leukemia ,Recommendations ,Leukemia relapse ,Treatment response ,Cancer staging ,Time factor ,European LeukemiaNet ,0302 clinical medicine ,Immunophenotyping ,Cancer Survivors ,hemic and lymphatic diseases ,Pathology ,Overall survival ,Molecular Targeted Therapy ,Registries ,Age of Onset ,Child ,Children ,Priority journal ,Chronic myeloid leukemia ,Stem cell transplantation ,Hematopoietic Stem Cell Transplantation ,Register ,Multicenter study ,3. Good health ,Chronic Myeloid Leukemia ,Imatinib ,Protein Tyrosine Kinase Inhibitor ,Clinical trial ,Haematopoiesis ,Retrospective study ,Treatment Outcome ,Oncology ,Molecularly targeted therapy ,030220 oncology & carcinogenesis ,Child, Preschool ,International registry ,Interphase-fish ,Cml patients ,Protein kinase inhibitor ,Cancer survivor ,Disease Progression ,Female ,Cancer chemotherapy ,Chronic myelogenous leukemia ,medicine.drug ,Human ,Adult ,Adverse event ,medicine.medical_specialty ,Adolescent ,Lymphoid blast crisis ,Major clinical study ,Blastic Phase ,Article ,03 medical and health sciences ,Internal medicine ,Advanced cancer ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Factual database ,Prospective study ,Disease exacerbation ,Mortality ,neoplasms ,Survival rate ,Protein tyrosine kinase inhibitor ,Protein Kinase Inhibitors ,Chronic myeloid leukaemia ,Neoplasm Staging ,Tyrosine kinase inhibitors ,Chemotherapy ,business.industry ,Prognostic-factors ,Infant ,Follow up ,Transplantation ,030104 developmental biology ,Onset age ,Preschool child ,Comparative study ,business ,Controlled study - Abstract
Background Chronic myeloid leukaemia (CML) is very rare in children. The aim of the study is to report the experience within the I-CML-Ped study in children and adolescents presenting at diagnosis with advanced phase disease and to describe their characteristics and outcomes. Methods Of 479 children and adolescents enrolled in the international registry for childhood chronic myeloid leukaemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735 ), 36 children (7.5%) presented at initial diagnosis with CML in advanced phase according to the European LeukemiaNet criteria. Results Nineteen (4%) patients were diagnosed in accelerated phase (CML-AP), and among the 17 patients (3.5%) diagnosed in blastic phase (CML-BP), 70% presented with lymphoid immunophenotype. Initial treatment of CML-AP/CML-BP consisted of tyrosine kinase inhibitors (TKIs) with or without chemotherapy, leading to complete haematologic response in 33 of 36 (92%) patients. Seventeen patients proceeded to haematopoietic stem cell transplantation. At the last follow-up, 18 of 19 patients with de novo CML-AP are alive in at least major molecular response (MMR) (n = 16), in progression (n = 1) or in molecular relapse (n = 1) and 13 of 17 patients with de novo CML-BP are alive in at least MMR. Five-year overall survival rates are 94% (95% confidence interval [CI]: 66%–99%) and 74% (95% CI: 44%–89%) for patients diagnosed in CML-AP and CML-BP, respectively. Conclusion Children with advanced phase at diagnosis of CML seem to have a better survival rate than that reported for advanced phases evolving under TKI treatment.
- Published
- 2018
9. Evaluation of lapatinib cytotoxicity and genotoxicity on MDA-MB-231 breast cancer cell line.
- Author
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Abo-Zeid, Mona A.M., Abo-Elfadl, Mahmoud T., and Gamal-Eldeen, Amira M.
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GENETIC toxicology , *CELL-mediated cytotoxicity , *TRIPLE-negative breast cancer , *CELL lines , *CANCER cells , *EPIDERMAL growth factor , *BREAST cancer - Abstract
• Lapatinib induced cytotoxic and genotoxic effects on MDA-MB-231 cell line. • Lapatinib IC 50 value was 32.5 μM after 24 h on MDA-MB-231 cells. • Lapatinib triggered extensive DNA damage as recorded with micronucleus test. • Laptinib reduced the EGFR protein expression and EGFR gene signals. • Lapatinib elevated the apoptotic cell death and as well TP53 gene signals. Lapatinib, one of the tyrosine kinase inhibitors (TKIs), is used to reduce epidermal growth factor family proteins overexpression. This study aims to assess the cytotoxic and genotoxic effects of lapatinib on the triple negative breast cancer cell line "MDA-MB-231". We investigated the cytotoxicity of lapatinib by MTT assay, mode of cell death using apoptosis-necrosis assay, DNA damage using micronucleus test, EGFR protein expression by immunocytochemistry, and assessed its effect on EGFR (7p11.2 locus) and TP53 (17p13 locus) genes using interphase-FISH technique. Lapatinib induced cytotoxicity on MDA-MB-231 cell line by elevating the concentration and its IC 50 value was 32.5 μM after 24 h. Lapatinib increased apoptotic cells and micronuclei in binucleated cells gradually by increasing the concentration for 24 h. The EGFR protein expression was reduced by double fold that expressed in non-treated cells. Lapatinib enhanced deletion of EGFR gene signals highly significantly from the lowest concentration. Alternatively, lapatinib amplified signals of TP53 gene effectively by raising the concentration. In conclusion, lapatinib induced cytotoxic and genotoxic effects on MDA-MB-231 cell line. However, laptinib reduced the EGFR protein expression and EGFR signals, it raised the apoptotic cells and TP53 gene signals, which triggered extensive DNA damage. Therefore, lapatinib is an effective TKI in triple negative breast cancer cells as elucidated by its mode of cell death. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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10. Glioblastomas with Oligodendroglial Component – Common Origin of the Different Histological Parts and Genetic Subclassification
- Author
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Barbara Klink, Ben Schlingelhof, Martin Klink, Karen Stout-Weider, Stephan Patt, and Evelin Schrock
- Subjects
Adult ,Male ,Cancer Research ,Interphase-FISH ,genetic subclassification ,Oligodendroglioma ,Pathology and Forensic Medicine ,Imaging, Three-Dimensional ,Image Processing, Computer-Assisted ,Humans ,genetics ,In Situ Hybridization, Fluorescence ,RC254-282 ,Aged ,CGH ,QH573-671 ,Brain Neoplasms ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell Biology ,General Medicine ,Middle Aged ,oligodendroglial component ,GBMO ,Molecular Medicine ,Female ,Other ,Glioblastoma ,Cytology - Abstract
Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data.Methods: The oligodendroglial and the “classic” glioblastoma parts of 13 GBMO were analyzed separately by interphase fluorescence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue.Results: We identified four distinct genetic subtypes in 13 GBMOs: an “astrocytic” subtype (9/13) characterized by +7/−10; an “oligodendroglial” subtype with −1p/−19q (1/13); an “intermediate” subtype showing +7/−1p (1/13), and an “other” subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part.Conclusion: Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients.
- Published
- 2010
11. Detection of three common translocation breakpoints in non-Hodgkin's lymphomas by fluorescence in situ hybridization on routine paraffin-embedded tissue sections
- Author
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Ed Schuuring, Eugenia Haralambieva, K Kleiverda, Philip M. Kluin, David Y. Mason, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
non-Hodgkin's lymphoma ,Pathology ,medicine.medical_specialty ,ABL ,Follicular lymphoma ,Genes, myc ,In situ hybridization ,Lymphoma, Mantle-Cell ,Biology ,HEMATOLOGICAL MALIGNANCIES ,Translocation, Genetic ,INTERPHASE-FISH ,Pathology and Forensic Medicine ,FISH ,CHROMOSOMAL TRANSLOCATIONS ,medicine ,C-MYC ,Humans ,Lymphoma, Follicular ,In Situ Hybridization, Fluorescence ,translocations ,BURKITTS-LYMPHOMA ,Paraffin Embedding ,medicine.diagnostic_test ,Lymphoma, Non-Hodgkin ,Breakpoint ,Cytogenetics ,paraffin sections ,medicine.disease ,Burkitt Lymphoma ,SYNOVIAL SARCOMA ,GENE ,Genes, bcl-1 ,Non-Hodgkin's lymphoma ,Lymphoma ,Genes, bcl-2 ,MANTLE-CELL LYMPHOMA ,Mantle cell lymphoma ,FOLLICULAR LYMPHOMA ,Algorithms ,Fluorescence in situ hybridization - Abstract
Non-random chromosomal translocations are specifically involved in the pathogenesis of many non-Hodgkin's lymphomas and have clinical implications as diagnostic and/or prognostic markers. Their detection is often impaired by technical problems, including the distribution of the breakpoints over large genomic areas. This study reports a fluorescence in situ hybridization (FISH) method which allows the detection of specific chromosomal breakpoints in tissue sections from routinely fixed, paraffin-embedded samples. Hybridization was performed after demasking the DNA. Previously validated locus-specific probes (cosmids, PACs) flanking the BCL1, BCL2 regions and similar new probes for the MYC breakpoint region were used. The cases studied were five mantle cell lymphomas (MCL) and five follicular lymphomas (FL), selected on the basis of a previously proved t(11;14) and t(14;18) and five randomly chosen Burkitt's lymphomas (BL), as well as 21 negative control samples. In all samples, hybridization signals of sufficient intensity were obtained. Three different algorithms were used to score the hybridization signals in tissue sections, two of them taking into account the nuclei and their signal distribution indicative of chromosomal break, and one only considering the colocalization or segregation of the signals. In control tissues, these algorithms resulted in cut-off levels of 9.1%, 1.3%, or 10.0%. In the 15 lymphoma samples the percentages of abnormal cells/signals ranged from 28% to 80%, 13% to 49%, and 40% to 70%, respectively. The results indicate that small locus-specific probes can be used in FISH for regular detection of translocation breakpoints on routine paraffin tissue sections. Copyright (C) 2002 John Wiley Sons, Ltd.
- Published
- 2002
12. Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH
- Author
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Mieczyslaw Gajda, M. Sternal, S. Matthes, Jimsgene Sanjmyatav, Muehr M, Kerstin Junker, Heiko Wunderlich, D. Sava, and Marc-Oliver Grimm
- Subjects
Adult ,Male ,Cancer Research ,Disease free survival ,Pathology ,medicine.medical_specialty ,Kaplan-Meier Estimate ,Risk Assessment ,Disease-Free Survival ,disease progression ,Area under curve ,Medicine ,Humans ,metastasis ,Neoplasm Metastasis ,Carcinoma, Renal Cell ,Interphase ,Molecular Diagnostics ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,Chromosome Aberrations ,High risk patients ,business.industry ,clear cell RCC ,Middle Aged ,medicine.disease ,Prognosis ,Kidney Neoplasms ,Clear cell renal cell carcinoma ,Oncology ,ROC Curve ,interphase-FISH ,Area Under Curve ,genetic markers ,%22">Fish ,Identification (biology) ,Neoplasm staging ,Female ,business - Abstract
Background: The aim of this study was to examine the prognostic value of four significant aberrations based on our previous studies by array-CGH to develop a prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal cell carcinomas (ccRCC). Methods: Fluorescence-in situ-hybridisation experiments were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The mean/median follow up of patients was 59/54 months. Commercially available FISH probes were used for each critical chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA) was calculated for each tumour based on the specific genomic alterations. Results: Total number of specific aberrations was the best predictor of metastasis (area under the curve (AUC)=0.814) compared with single aberrations (AUC: 0.619–0.708) and to 11 different combinations of these 4 aberrations in the receiver operating characteristic curve analysis. Total number of specific aberrations, tumour grade and tumour size were independent predictors of metastasis in the multivariate analysis (P
- Published
- 2013
13. Molekularzytogenetische Untersuchungen von klonalen Chromosomenveränderungen im Knochenmark und in mononukleären Zellen des peripheren Blutes von Fanconi Anämie Patienten: Nachweis und klinische Relevanz
- Author
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Huber, Stefanie Teresa
- Subjects
Interphase-FISH ,AML ,chromosomal aberrations ,MDS ,comparative genomic hybridization ,fanconi anemia ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
Titelblatt, Inhaltsverzeichnis, Zusammenfassung, Danksagung, Lebenslauf und Eidesstattliche Erklärung Einleitung Material und Methoden Ergebnisse Diskussion Literaturverzeichnis Anhang, In der vorliegenden Arbeit wurden 43 Patienten mit Fanconi Anämie (FA) untersucht, deren Diagnose anhand der typischen erhöhten Chromosomenbrüchigkeit gegenüber Mitomycin C gesichert war. Die vorhandenen Daten der konventionellen Zytogenetik und der CGH zeigten bei 17 dieser Patienten einen Zugewinn von chromosomalem Material für die allen gemeinsame chromosomale Region 3q26q29 und bei 9 Patienten den Verlust chromosomalen Materials für die diesen Patienten gemeinsame chromosomale Region 7q21qter. Zuvor wurde in der Literatur nie von einer derart großen Anzahl von Fanconi Anämie Patienten mit Aberration von Chromosom 3q berichtet. Um diese Aberrationen schnell detektieren zu können und eine quantitative Aussage bezüglich dieser klonalen chromosomalen Aberrationen treffen sowie deren zeitlichen Verlauf beurteilen zu können, wurde ein Interphase-FISH Panel für Chromosom 3 und 7 etabliert und angewendet. Hierdurch konnten sowohl die Aberration von Chromosom 7 und die partielle Trisomie 3q als auch die durch die CGH nicht analysierte partielle Tetrasomie 3q sicher detektiert werden. Dabei wurden I-FISH Untersuchungen an Blut- und Knochenmarkproben durchgeführt und es konnte erstmals nachgewiesen werden, dass die klonalen chromosomalen Aberrationen der FA Patienten in den mononukleären Zellen des peripheren Bluts vorliegen und ein großer Zusammenhang zwischen den I-FISH Analysen von Knochenmark und peripherem Blut besteht. Die Aberrationen von Chromosom 3 und 7, welche zumeist als kombinierte Aberrationen auftraten, waren im Gegensatz zu anderen Aberrationen, welche bisher für FA Patienten in der Literatur beschrieben sind, nicht transient und zeigten darüber hinaus einen erheblichen Proliferationsvorteil. Durch unsere Untersuchungen konnten erstmals zwei spezifische Aberrationen bei FA Patienten detektiert werden, welche einen direkten Zusammenhang mit dem Auftreten eines MDS oder einer AML aufweisen und einen negativen Risikofaktor bezüglich des Überlebens der FA Patienten darstellen. Deswegen sollten alle FA Patienten molekularzytogenetisch untersucht werden, um diese Aberrationen frühzeitig zu detektieren und im Falle der Detektion dieser Aberrationen eine baldige Stammzelltransplantation erwogen werden., In the present study we analyzed 43 patients with Fanconi Anemia (FA), whose diagnosis was proven by the typical increased chromosome breakage after mitomycin c treatment. The existing data of classical cytogenetics and comparative genomic hybridization (CGH) showed additional chromosomal material for the common chromosomal region of 3q26q29 in 17 patients and a loss of chromosomal material for the common chromosomal region 7q21qter in 9 patients. In the literature, never before such a large number of Fanconi Anemia patients with aberrations of chromosome 3q was reported. For a fast detection of these aberrations and for a quantitative statement of clonal chromosomal aberrations, as well as a follow-up over the time, an Interphase-FISH panel for chromosomes 3 and 7 was established and applied. Hereby, aberration of chromosome 7 and partial trisomy 3q as well as partial tetrasomy 3q, which was not detected by CGH, could be reliable detected. I-FISH analysis were made on blood- and bone marrow samples and for the first time it could be demonstrated that clonal chromosomal aberrations of FA patients exist in the mononuclear cells of peripheral blood. Furthermore, there was a great connection between I-FISH analysis of samples of bone marrow and peripheral blood. Aberrations of chromosome 3 and 7, which mostly appeared as combined aberrations, were not transient in contrast to other aberrations which were described in the literature so far and beyond that showed a considerable proliferation advantage. By our investigations, two specific aberrations in FA patients could be detected for the first time which showed a direct connection with the appearance of AML or MDS and represent an adverse risk factor for survival of FA patients. Therefore, all FA patients should be screened by molecular cytogenetic analysis to detect these aberrations early. In case of detection of these aberrations, an early hematopoietic stemm cell transplantation should be considered.
- Published
- 2006
- Full Text
- View/download PDF
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