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Genomic Profile (genomic + profile)
Selected AbstractsTNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphomaGENES, CHROMOSOMES AND CANCER, Issue 1 2008Keiichiro Honma The genomic aberrations in extra nodal marginal zone B cell lymphoma vary according to their anatomical origin. This polarization is a reflection of the participation of different genes in the lymphomagenesis of marginal zone B cell lymphoma. We previously demonstrated by means of genome-wide array comparative genomic hybridization (CGH) that the genomic profile of ocular adnexal marginal zone B cell lymphoma is distinct from that of pulmonary or nodal marginal zone B cell lymphoma. The novel finding was a recurrent deletion of a 2.9-Mb region at chromosome band 6q23.3-q24.1, including homozygous loss, in ocular adnexal marginal zone B cell lymphoma. For a more detailed examination of the deletions of 6q23.3-24.1, we used contig bacterial artificial chromosome (BAC) array CGH, containing 24 BAC clones covering the 2.9-Mb region, to analyze nine cases with 6q23.3-q24.1 loss. We narrowed the minimal common region down to a length of 586 kb with two genes and four expressed sequence tags (ESTs). All of these genes and ESTs were subjected to RT-PCR and real-time quantitative RT-PCR. Correlation between genomic loss and expression level was found only for TNFAIP3, demonstrating that TNFAIP3 is a target gene of 6q deletion in ocular adnexal marginal zone B cell lymphoma. TNFAIP3 is an inhibitor of NF-kB signaling so that loss of this gene may play an important role in lymphomagenesis and suggests that TNFAIP3 may act as a tumor suppressor gene in ocular adnexal marginal zone B cell lymphoma. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source] Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriersHEPATOLOGY RESEARCH, Issue 4 2009Tadashi Ikegami Aim:, A large cohort study in Japan revealed that the specific viral profile may influence the fulminant outcome in acute hepatitis B virus (HBV) infections, while the genetic influence on outcome has not been clarified in patients with acute exacerbation of chronic liver disease caused by HBV. We experienced a case of fatal liver failure that developed as the result of chronic HBV infection. To determine possible genetic factor involving acute exacerbation, genetic analysis of serum from the patient and his siblings was performed. Methods:, HBV subgenotype as well as pre-core/core-promoter mutations of samples mentioned above were determined. Results:, Patient had HBV-Bj with pre-core (1896/1899) and core-promoter (1762/1764) mutations, the genomic profile frequently seen in fulminant hepatitis caused by acute HBV infection. Conclusion:, This result suggests that determination of the HBV subgenotype and pre-core/core promoter mutations could provide a rationale for development of a treatment strategy in asymptomatic HBV carriers. [source] Cutaneous type adult T-cell leukemia/lymphoma is a characteristic subtype and includes erythema/papule and nodule/tumor subgroupsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Tomoko Miyata Abstract We first analyzed the genomic profile of cutaneous type adult T-cell leukemia/lymphoma (ATLL) in an attempt to clarify its clinical and biological characteristics. Genomic gains of 1p, 7q and 18q and loss of 13q were frequently detected. Gain of 1p36.33-32 or loss of 13q33.1-3 indicated poor prognosis. Among cases with generalized lesions, erythema/papule or nodule/tumor cases showed a distinct genomic profile, indicating that these 2 groups were biologically different and developed via different genetic pathways. Furthermore, cases with generalized nodule/tumor lesions tended to progress to aggressive ATLL. [source] Diversity of genome profiles in malignant lymphomaCANCER SCIENCE, Issue 3 2010Masao Seto (Cancer Sci 2010; 101: 573,578) Characteristic chromosome translocations are associated with specific disease entities, and are known to play a pivotal role in lymphoma development. Chromosome translocation alone, however, is not sufficient to produce tumors. Factors including the microenvironment and epigenetic and genetic alterations other than chromosome translocations have been shown to play a role in lymphoma development. Follicular lymphoma cells proliferate in close contact with follicular dendritic cells. Mucosa-associated lymphoid tissue (MALT) lymphoma cells proliferate at the marginal zone area of reactive follicles which are formed by preceding chronic inflammation. The importance of genetic alterations other than chromosome translocation has been recognized since the introduction of array comparative genomic hybridization (array CGH). Variations in the genomic profile among patients with the same disease entity have been found by array CGH analyses. These variations indicate that multiple genetic pathways leading to the development of lymphomas may exist and hence result in the variable clinicopathological features observed. [source] Valproic acid blood genomic expression patterns in children with epilepsy , a pilot studyACTA NEUROLOGICA SCANDINAVICA, Issue 3 2004Y. Tang Objective , Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy. Materials and methods , Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients). Results , The expression of 461 genes was altered in VPA patients (n = 11) compared with drug free patients (n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy (n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures (n = 3) and drug free seizure patients (n = 7). Conclusion , VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity. [source] Papillary and muscle invasive bladder tumors with distinct genomic stability profiles have different DNA repair fidelity and KU DNA-binding activitiesGENES, CHROMOSOMES AND CANCER, Issue 4 2009Johanne Bentley Low-grade noninvasive papillary bladder tumors are genetically stable whereas muscle invasive bladder tumors display high levels of chromosomal aberrations. As cells deficient for nonhomologous end-joining (NHEJ) pathway components display increased genomic instability, we sought to determine the NHEJ repair characteristics of bladder tumors and correlate this with tumor stage and grade. A panel of 13 human bladder tumors of defined stage and grade were investigated for chromosomal aberrations by comparative genomic hybridization and for NHEJ repair fidelity and function. Repair assays were conducted with extracts made directly from bladder tumor specimens to avoid culture-induced phenotypic alterations and selection bias as only a minority of bladder tumors grow in culture. Four noninvasive bladder tumors (pTaG2), which were genetically stable, repaired a partially incompatible double-strand break (DSB) by NHEJ-dependent annealing of termini and fill-in of overhangs with minimal loss of nucleotides. In contrast, four muscle invasive bladder cancers (pT2-3G3), which displayed gross chromosomal rearrangements, repaired DSBs in an error-prone manner involving extensive resection and microhomology association. Four minimally invasive bladder cancers (pT1G3) had characteristics of both repair types. Error-prone repair in bladder tumors correlated with reduced KU DNA-binding and loss of TP53 function. In conclusion, there were distinct differences in DSB repair between noninvasive papillary tumors and higher stage/grade invasive cancers. End-joining fidelity correlated with stage and was increasingly error-prone as tumors became more invasive and KU binding activity reduced; these changes may underlie the different genomic profiles of these tumors. © 2008 Wiley-Liss, Inc. [source] Use of magnetic beads to extract fungal DNAMYCOSES, Issue 1 2005E. Faggi Summary Authors compare two methods of extracting DNA from different fungi: the classic method with phenol/chloroform (P/C) and that with magnetic beads. Both were tested on Candida albicans and Cryptococcus neoformans var. neoformans, belonging to the yeast group and Microsporum canis, M. gypseum, Trichophyton rubrum, T. interdigitale, T. ajelloi, Epidermophyton floccosum, belonging to the dermatophytes group. Extraction products underwent polymerase chain reaction (PCR) fingerprinting with the appropriate primers to point out any disagreement in the genomic profiles. After having determined that the genomic profiles obtained from the DNA extracted from the same strain with the two methods correspond perfectly, the authors concluded that the extraction method with magnetic beads from fungal cells is simpler and quicker than with P/C extraction, greatly facilitating the obtainment of fungal DNA. [source] Isolation of Trichosporon in a hematology wardMYCOSES, Issue 1 2005Gabriella Pini Summary During mycologic monitoring of the air in a hematology ward, we found massive air contamination caused by Trichosporon asahii, both in the room where neutropenic patients were staying and the corridor immediately outside the room. This fungal species had never been isolated in previous samplings. The urine culture taken from one of the patients in this room, whose urinary catheter had been removed immediately prior to air sampling, resulted positive for T. asahii. Both macroscopic and microscopic morphologic observation was insufficient for confirming the hypothesis of a close relationship between the strains isolated from the patient, from the air in the room and corridor. Therefore, we used genomic typing with random amplified polymorphic DNA (RAPD). The five primers used, (GTG)5, (GACA)4, M13, OPE01, RC08, produced different patterns of polymerase chain reaction (PCR) products; the genomic profiles obtained with the same primer, however, resulted perfectly superimposable for all the strains. This result led us to conclude that the massive air contamination caused by T. asahii can have effectively been determined by the removal of the urinary catheter from the patient who presented an asymptomatic infection caused by this microorganism. [source] Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signaturesCANCER, Issue 16 2009Chiara Braconi MD Abstract BACKGROUND: The presence of vascular invasion in hepatocellular cancer (HCC) correlates with prognosis, and is a critical determinant of both the therapeutic approach and the recurrence or intrahepatic metastases. The authors sought to identify candidate therapeutic agents capable of targeting the invasive phenotype in HCC. METHODS: A gene expression signature associated with vascular invasion derived from 81 human cases of HCC was used to screen a database of 453 genomic profiles associated with 164 bioactive molecules using the connectivity map. Candidate agents were identified by their inverse correlation to the query gene signature. The efficacy of the candidate agents to target invasion was experimentally verified in PLC/PRF-5 and HepG2 HCC cells. RESULTS: The gene signature associated with vascular invasion in HCC comprised of 47 up-regulated and 26 down-regulated genes. Computational bioinformatics analysis revealed several putative candidates, including resveratrol and 17-allylamino-geldanamycin (17-AAG). Both of these agents reduced HCC cell invasion at noncytotoxic concentrations. 17-AAG, a heat shock protein 90 (HSP-90) inhibitor, was shown to modulate the expression of several diverse cancer-associated genes, including ADAMTS1, part of the query signature, and maspin, an HSP-90,associated protein with a tumor suppressor role in HCC. CONCLUSIONS: Candidates for further evaluation as therapies to limit invasion in HCC have been identified using a computational bioinformatics analysis of phenotype-associated gene expression. Phenotype targeting using genomic profiling is a rational approach for drug discovery. Therapeutic strategies targeting a defined cancer-associated phenotype can be identified without a detailed knowledge of individual downstream targets. Cancer 2009. © 2009 American Cancer Society. [source] | ||||||||||