RESUMO
BACKGROUND: Cutaneous lymphomas (CL) represent a clinically defined group of extranodal non-Hodgkin lymphomas harbouring heterogeneous and incompletely delineated molecular aberrations. Over the past decades, molecular studies have identified several chromosomal aberrations, but the interpretation of individual genomic studies can be challenging. OBJECTIVE: With a comprehensive meta-analysis, we aim to delineate genomic alterations for different types of CL and propose a more accurate classification in line with their various pathogenicity. METHODS: We searched PubMed and ISI Web of Knowledge for publications from 1996 to 2016 reporting the investigation of CL for genome-wide copy number alterations, by means of comparative genomic hybridization techniques and whole-genome sequencing and whole-exome sequencing. We then extracted and remapped the available copy number variation (CNV) data from these publications with the same pipeline and performed clustering and visualisation to aggregate samples of similar CNV profiles. RESULTS: For 449 samples from 22 publications, CNV data were accessible for sample based meta-analysis. Our findings illustrate structural and numerical chromosomal imbalance patterns. Most frequent CNAs were linked to oncogenes or tumour suppressor genes with important roles in the course of the disease. CONCLUSION: Summary profiles for genomic imbalances, generated from case-specific data, identified complex genomic imbalances, which could discriminate between different subtypes of CL and promise a more accurate classification. The collected data presented in this study are publicly available through the 'Progenetix' online repository.
Assuntos
Variações do Número de Cópias de DNA , Linfoma não Hodgkin/genética , Neoplasias Cutâneas/genética , Aberrações Cromossômicas , HumanosRESUMO
Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstand high doses of irradiation and to prevent irradiation-induced apoptosis. However, the underlying regulatory basis for this phenotype is not well understood. Here, a kinetic network analysis based on reverse phase protein arrays (RPPAs) in combination with extensive western blot and cell culture analyses was employed to decipher the cytoplasmic and nuclear signaling networks and to identify possible antiapoptotic pathways. This analysis identified activation of known DNA damage response pathways (e.g., phosphorylation of MKK3/6, p38, MK2, Hsp27, p53 and Chk1) as well as of prosurvival (e.g., MEK-ERK, cAMP response element-binding protein (CREB), protein kinase C (PKC)) and antiapoptotic markers (e.g., Bad, Bcl-2). Interestingly, PKC family members were activated early upon irradiation, suggesting a regulatory function in the ionizing radiation (IR) response of these cells. Inhibition or downregulation of PKC in primary human fibroblasts caused IR-dependent downregulation of the identified prosurvival (CREB phosphorylation) and antiapoptotic (Bad phosphorylation, Bcl-2) markers and thus lead to a proliferation stop and to apoptosis. Taken together, our analysis suggests that cytoplasmic PKC signaling conditions IR-stressed MRC-5 and IMR-90 cells to prevent irradiation-induced apoptosis. These findings contribute to the understanding of the cellular and nuclear IR response and may thus eventually improve the efficacy of radiotherapy and help overcome tumor radioresistance.
Assuntos
Apoptose/efeitos da radiação , Fibroblastos/citologia , Proteína Quinase C/metabolismo , Radiação Ionizante , Proteína de Ligação a CREB/metabolismo , Análise por Conglomerados , Dano ao DNA/efeitos da radiação , Reparo do DNA , Regulação para Baixo , Fibroblastos/metabolismo , Humanos , Fosforilação , Mapas de Interação de Proteínas , Proteoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.
Assuntos
Carcinoma Ductal Pancreático/genética , Deleção Cromossômica , Cromossomos Humanos Par 4 , Neoplasias Pancreáticas/genética , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 8 , Cromossomos Humanos Par 9 , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Análise de SobrevidaRESUMO
The MUC1 gene is aberrantly overexpressed in approximately 90% of human breast cancers. Several studies have shown that MUC1 overexpression is due to transcriptional regulatory events. However, the importance of gene amplification as a mechanism leading to the increase of MUC1 expression in breast cancer has been poorly characterized. The aim of this study was to evaluate the role of MUC1 gene amplification and protein expression in human breast cancer development. By means of real-time quantitative polymerase chain reaction and immunohistochemical methods, 83 breast tissue samples were analyzed for MUC1 gene amplification and protein expression. This analysis showed MUC1 genomic amplification and a positive association with the histopathological group in 12% (1 out of 8) of benign lesions and 38% (23 out of 60) of primary invasive breast carcinoma samples (P = 0.004). Array-comparative genomic hybridization meta-analysis of 886 primary invasive breast carcinomas obtained from 22 studies showed MUC1 genomic gain in 43.7% (387 out of 886) of the samples. Moreover, we identified a highly statistical significant association between MUC1 gene amplification and MUC1 protein expression assessed by immunohistochemistry and Western blot test (P < 0.0001). In conclusion, this study demonstrated that MUC1 copy number increases from normal breast tissue to primary invasive breast carcinomas in correlation with MUC1 protein expression.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Amplificação de Genes , Mucina-1/genética , Western Blotting , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Mucina-1/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
MOTIVATION: One of the mutational processes that has been monitored genome-wide is the occurrence of regional DNA copy number alterations (CNAs), which may lead to deletion or over-expression of tumor suppressors or oncogenes, respectively. Understanding the relationship between CNAs and different cancer types is a fundamental problem in cancer studies. RESULTS: This article develops an efficient method that can accurately model the progression of the cancer markers and reconstruct evolutionary relationship between multiple types of cancers using comparative genomic hybridization (CGH) data. Such modeling can lead to better understanding of the commonalities and differences between multiple cancer types and potential therapies. We have developed an automatic method to infer a graph model for the markers of multiple cancers from a large population of CGH data. Our method identifies highly related markers across different cancer types. It then builds a directed acyclic graph that shows the evolutionary history of these markers based on how common each marker is in different cancer types. We demonstrated the use of this model in determining the importance of markers in cancer evolution. We have also developed a new method to measure the evolutionary distance between different cancers based on their markers. This method employs the graph model we developed for the individual markers to measure the distance between pairs of cancers. We used this measure to create an evolutionary tree for multiple cancers. Our experiments on Progenetix database show that our markers are largely consistent to the reported hot-spot imbalances and most frequent imbalances. The results show that our distance measure can accurately reconstruct the evolutionary relationship between multiple cancer types.
Assuntos
Hibridização Genômica Comparativa , Modelos Genéticos , Biomarcadores Tumorais/genética , Dosagem de Genes , Humanos , Neoplasias/genética , Neoplasias/patologia , FilogeniaRESUMO
Burkitt lymphoma (BL) has a characteristic clinical presentation, morphology, immunophenotype and primary chromosomal aberration, that is, the translocation t(8;14)(q24;q32) or its variants. However, diagnostic dilemmas may arise in daily practice due to overlap of BL with subsets of other aggressive, mature B-cell lymphomas such as diffuse large B-cell lymphomas (DLBCL). Recently, two gene expression studies have described a distinct molecular profile for BL, but also showed the persistence of some cases intermediate between BL and DLBCL. An alternative approach to define BL is to consider (cyto)genetic data, in particular chromosomal abnormalities other than the t(8;14) or its variants. In this review the 'Mitelman Database of Chromosome Aberrations in Cancer,' harboring the majority of all published neoplasia-related karyotypes, was explored to define a cytogenetic profile of 'true' BL. This core subset of BL showed a very low complexity of chromosomal abnormalities with 40% of the cases having the IG-MYC fusion as the sole abnormality. In the remaining cases, additional recurrent but partially exclusive abnormalities included gains at chromosomes 1q, 7 and 12, and losses of 6q, 13q32-34 and 17p. Within the core subset, no differences were found between pediatric and adult patients. In addition, the genetic profile of the core subset was significantly different from BL with an 8q24 breakpoint not affecting one of the three immunoglobulin loci, BL with a translocation involving 18q21/BCL2, 3q27/BCL6 or 11q13/BCL1, additionally to a breakpoint at 8q24/MYC, and from other morphological types of lymphomas with an 8q24/MYC breakpoint. These groups showed a higher cytogenetic complexity than the core subset of BL. BL without a detectable 8q24/MYC breakpoint might be heterogeneous and deserves further studies. We suggest that, concordant with the WHO classification to be published in 2008, the diagnosis of BL should be restricted to cases with expression of CD10 and BCL6, absence or very weak expression of BCL2 protein, a homogeneously very high proliferation index and a proven IG-MYC translocation without evidence of a chromosomal translocation typical for other lymphoma entities. In addition, a high number of nonspecific cytogenetic abnormalities should suggest need for a critical review of the diagnosis of BL.
Assuntos
Linfoma de Burkitt/genética , Translocação Genética , Linfoma de Burkitt/classificação , Linfoma de Burkitt/diagnóstico , Cromossomos Humanos Par 8 , Citogenética/história , Perfilação da Expressão Gênica , História do Século XX , História do Século XXI , Humanos , Linfoma/classificação , Linfoma/diagnóstico , Linfoma/genéticaRESUMO
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive lymphoma derived from mature T cells, which is, in most cases, characterized by the presence of an inv(14)(q11q32)/t(14;14)(q11;q32) and a characteristic pattern of secondary chromosomal aberrations. DNA microarray technology was employed to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor-derived peripheral blood cell samples, with five highly purified inv(14)/t(14;14)-positive T-PLL blood samples. Between the two experimental groups, 734 genes were identified as differentially expressed, including functionally important genes involved in lymphomagenesis, cell cycle regulation, apoptosis and DNA repair. Notably, the differentially expressed genes were found to be significantly enriched in genomic regions affected by recurrent chromosomal imbalances. Upregulated genes clustered on chromosome arms 6p and 8q, and downregulated genes on 6q, 8p, 10p, 11q and 18p. High-resolution copy-number determination using single nucleotide polymorphism chip technology in 12 inv(14)/t(14;14)-positive T-PLL including those analyzed for gene expression, refined chromosomal breakpoints as well as regions of imbalances. In conclusion, combined transcriptional and molecular cytogenetic profiling identified novel specific chromosomal loci and genes that are likely to be involved in disease progression and suggests a gene dosage effect as a pathogenic mechanism in T-PLL.
Assuntos
Inversão Cromossômica , Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 14 , Perfilação da Expressão Gênica , Leucemia Prolinfocítica/genética , Leucemia de Células T/genética , Polimorfismo de Nucleotídeo Único , Apoptose , Complexo CD3/biossíntese , Aberrações Cromossômicas , Reparo do DNA , Progressão da Doença , Dosagem de Genes , Humanos , Análise de Sequência com Séries de OligonucleotídeosRESUMO
UNLABELLED: Through sequencing projects and, more recently, array-based expression analysis experiments, a wealth of genetic data has become accessible via online resources. In contrast, few of the (molecular-) cytogenetic aberration data collected in the last decades are available in a format suitable for data mining procedures. www.progenetix.net is a new online repository for previously published chromosomal aberration data, allowing the addition of band-specific information about chromosomal imbalances to oncologic data analysis efforts. AVAILABILITY: http://www.progenetix.net CONTACT: mbaudis@stanford.edu
Assuntos
Aberrações Cromossômicas , Bases de Dados de Ácidos Nucleicos , Internet , CitogenéticaRESUMO
Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's Lymphoma, which has been recognized as a distinct disease entity. We performed a comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative genomic hybridization (CGH), the most common aberrations were gains of chromosome arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based on the limited resolution of CGH, this technique may underestimate the real incidence of aberrations. Therefore, we also did an interphase cytogenetic study with eight DNA probes mapping to chromosome regions frequently altered in B-cell lymphomas. With this approach, both 9p and Xq gains were found in more than 70% of cases (75% and 87%, respectively). The findings were compared with results obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six of the 308 cases, and only one of these lymphomas with 9p gains was not primarily extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence in situ hybridization data). We also present a novel MBL cell line, MedB-1, which carries the genetic aberrations characteristic of this entity.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos Par 9/genética , Análise Citogenética , Linfoma de Células B/genética , Neoplasias do Mediastino/genética , Células Tumorais Cultivadas/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Linfoma de Células B/patologia , Masculino , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico/métodosAssuntos
Linfoma não Hodgkin/genética , Hibridização de Ácido Nucleico/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Cromossomos Humanos/genética , Cromossomos Humanos/ultraestrutura , Ciclofosfamida/administração & dosagem , DNA de Neoplasias/genética , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Tábuas de Vida , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Metáfase , Análise de Sequência com Séries de Oligonucleotídeos , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Estudos Prospectivos , Análise de Sobrevida , Vincristina/administração & dosagemRESUMO
Cytogenetic methods have become increasingly important tools for both research in hematological malignancies and for the diagnostic workup of leukemias and lymphomas. The knowledge about specific chromosomal aberrations has been an essential prerequisite for the identification of pathogenetically relevant genes. Important examples are molecular genetic analyses of the breakpoint regions in chromosomal translocations, which resulted in the detection of protooncogenes such as ABL in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) [t(9,22)(q34;q11)], or MYC in Burkitt's lymphoma [t(8;14)(q24;q32); for a review see refs. 1 and 2].
RESUMO
Until now, few data on additional chromosomal aberrations in t(11;14)-positive mantle cell lymphomas (MCLs) have been published. We analyzed 39 t(11;14)-positive MCLs by either comparative genomic hybridization (CGH; n = 8), fluorescence in situ hybridization (FISH) with a set of DNA probes detecting the most frequent aberrations in B-cell neoplasms (n = 12), or both techniques (n = 19). The t(11;14) was present in all cases. In 37 of 39 cases, chromosomal imbalances were found. In 27 cases, complex karyotypes, i.e., >/= 3 aberrations, were identified. The most frequent aberrations were losses of 13q14-21 or 13q32-34 (27 cases), 9p21 (16 cases), and 11q22-23 (12 cases) and gains of 3q26-29 (19 cases), 8q22-24 (11 cases), and 18q21-22 (9 cases). In 26% of cases (7 of 27) analyzed by CGH, a total of 10 high-level DNA amplifications were identified. Although in comparison with B-cell chronic lymphopcytic leukemia (B-CLL) MCL is characterized by a much higher complexity of chromosomal aberrations, there are striking similarities: 13q14 deletions were identified in more than 50% of both MCL and B-CLL cases. In contrast, in our CGH database containing 293 B-cell lymphomas, this aberration was found in only 11% of other nodal lymphomas. Even more strikingly, 11q deletions, which are present in 20%-30 % of MCL and B-CLL, were found very rarely in other nodal B-cell lymphomas (CGH: 1 of 208 cases; FISH: 1 of 69 cases). These data show that MCL is characterized by specific secondary aberrations and that there may be similarities in the pathogenesis of MCL and B-CLL. Genes Chromosomes Cancer 27:285-294, 2000.
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Leucemia Linfocítica Crônica de Células B/genética , Linfoma de Célula do Manto/genética , Translocação Genética/genética , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Feminino , Amplificação de Genes , Genes bcl-2/genética , Humanos , Hibridização in Situ Fluorescente , Interfase/genética , Cariotipagem , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido NucleicoRESUMO
Gene amplification is one of the molecular mechanisms resulting in the up-regulation of gene expression. In non-Hodgkin's lymphomas, such gene amplifications have been identified rarely. Using comparative genomic hybridization, a technique that has proven to be very sensitive for the detection of high-level DNA amplifications, we analyzed 108 cases of B-cell neoplasms (42 chronic B-cell leukemias, 5 mantle cell lymphomas, and 61 aggressive B-cell lymphomas). Twenty-four high-level amplifications were identified in 13% of the patients and mapped to 15 different genomic regions. Regions most frequently amplified were bands Xq26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times each). Amplification of several proto-oncogenes and a cell cycle control gene (N-MYC (two cases), BCL2, CCND2, and GLI) located within the amplified regions was demonstrated by Southern blot analysis or fluorescence in situ hybridization to interphase nuclei of tumor cells. These data demonstrate that gene amplifications in B-cell neoplasms are much more frequent than previously assumed. The identification of highly amplified DNA regions and genes included in the amplicons provides important information for further analyses of genetic events involved in lymphomagenesis.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 2 , DNA de Neoplasias/genética , Linfoma de Células B/genética , Cromossomo X , Proteínas de Ciclo Celular/genética , Mapeamento Cromossômico , Amplificação de Genes , Humanos , Hibridização de Ácido Nucleico , Proto-Oncogenes/genéticaRESUMO
Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII, and 13.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was loss on 22q (58%). In MII, aberrations most commonly identified were losses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9q (33%), and 17q (33%). In MIII, most of these alterations were found at similar frequencies. However, an increase in losses on 6q (53%), 10 (68%), and 14q (63%) was observed. In addition, 32% of MIII demonstrated loss on 9p. Homozygous deletions in the CDKN2A gene at 9p21 were found in 4 of 16 MIII (25%). Highly amplified DNA sequences were mapped to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor revealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q were found to be amplified in 1 MII and 8 MIII, involving 17q23 in all cases. Despite the high frequency of chromosomal aberrations in the MII and MIII investigated, none of these tumors showed mutations in exons 5-8 of the TP53 gene. On the basis of the most common aberrations identified in the various malignancy grades, a model for the genomic alterations associated with meningioma progression is proposed.
Assuntos
Genoma Humano , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos GenéticosRESUMO
Molecular cytogenetics provides a powerful link between molecular genetic analysis and chromosome morphology, allowing one to pinpoint structurally aberrant chromosome regions on the molecular level. Fluorescence in situ hybridization with selected DNA probes allows the design of efficient and sensitive tools for the diagnosis of chromosomal aberrations present in tumor cells. Comparative genomic hybridization (CGH) allows the identification of chromosomal imbalances in a comprehensive manner, and is applied to solid tumors and hematological malignancies in order to (i) identify clonal differences within a specimen, (ii) contribute to tumor classifications, (iii) identify recurrent chromosomal gains and losses as starting points for the characterization and isolation of pathogenetically relevant genes, such as proto-oncogenes and tumor suppressor genes respectively, (iv) identify imbalances of prognostic relevance, (v) detect high-copy-number amplification and other markers of genetic instability, and (vi) analyze chromosomal imbalances during tumor progression.
Assuntos
Aberrações Cromossômicas , Citogenética/métodos , Neoplasias/genética , Neoplasias/patologia , Mapeamento Cromossômico , Sondas de DNA , Progressão da Doença , Humanos , Hibridização In Situ/métodos , Hibridização in Situ Fluorescente/métodos , Neoplasias/fisiopatologia , Prognóstico , Translocação GenéticaRESUMO
We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.
Assuntos
Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Aberrações Cromossômicas , Neoplasias Renais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
In comparison to leukemias, the clinical relevance of chromosomal aberrations in non-Hodgkin's lymphoma (NHL) is not as well understood. This is primarily due to limitations of chromosomal banding techniques which have been the central methods for cytogenetic analysis. These techniques depend on the availability of fresh tumor tissue and the examination of metaphase cells which may not be representative for the major cell clone in vivo. In contrast, the new technique of comparative genomic hybridization (CGH) allows researchers to obtain a comprehensive view of chromosomal gains and losses by analyzing tumor DNA, which can be prepared from archival tissue samples. Results of CGH studies in three different types of lymphoproliferative disorders are outlined in this paper demonstrating that: (1) in chronic B cell leukemias, chromosomal aberrations are missed by banding analysis in a high proportion of cases, (2) CGH on paraffin-embedded tissue samples can be used for cytogenetic analysis within clinical multicenter trials and (3) DNA amplifications are more frequent in NHL than previously assumed. Thus, it can be expected that CGH will contribute both to the understanding of pathogenetic mechanisms and the identification of clinically relevant chromosome aberrations in NHL.
Assuntos
Aberrações Cromossômicas , Linfoma não Hodgkin/genética , Humanos , Hibridização In Situ , Leucemia Linfocítica Crônica de Células B/genéticaRESUMO
Amyloidosis is a severe complication of rheumatoid arthritis (RA). A restriction fragment length polymorphism (RFLP) using MspI for the serum amyloid P gene was recently found to be associated with amyloidosis in juvenile arthritis. The aim of our study was to determine whether this RFLP could serve as a genetic marker for the development of secondary amyloidosis in RA. The prevalence of this marker was determined in 4 groups of patients: patients with amyloidosis secondary to RA; with amyloidosis secondary to various diseases excluding RA; with RA but without amyloidosis; adult controls without any known disease related to reactive amyloidosis. No significant differences were seen between these 4 groups with relation to this polymorphism, so that it cannot serve as a genetic marker for amyloidosis complicating RA in our population.