Search results for "Gene Rearrangement"
showing 10 items of 55 documents
Settling Down: The Genome of Serratia symbiotica from the Aphid Cinara tujafilina Zooms in on the Process of Accommodation to a Cooperative Intracell…
2014
Particularly interesting cases of mutualistic endosymbioses come from the establishment of co-obligate associations of more than one species of endosymbiotic bacteria. Throughout symbiotic accommodation from a free-living bacterium, passing through a facultative stage and ending as an obligate intracellular one, the symbiont experiences massive genomic losses and phenotypic adjustments. Here, we scrutinized the changes in the coevolution of Serratia symbiotica and Buchnera aphidicola endosymbionts in aphids, paying particular attention to the transformations undergone by S. symbiotica to become an obligate endosymbiont. Although it is already known that S. symbiotica is facultative in Acyrt…
Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation
2000
The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR beta chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A Vbeta8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at …
MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L
2011
SummaryThe histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-a…
HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segm…
1996
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes wit…
Central nervous system involvement in ALK-rearranged NSCLC : promising strategies to overcome crizotinib resistance
2016
ABSTRACT: Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibito…
Prevalence and Clinical Outcomes for Patients With ALK Gene Rearrangement in Europe: Preliminary Results from the European Thoracic Oncology Platform…
2012
ABSTRACT Background The prevalence of ALK gene rearrangement (ALK+) in European patients with non-small cell lung cancer (NSCLC) is unknown. The Lungscape project provides a platform to evaluate its expression and clinical significance in a large cohort of patients with resected NSCLC from 13 European sites in 11 countries. Methods Participating sites retrospectively identified cases of NSCLC with clinical demographic and outcome data, and available tissue for research according to predefined protocol criteria. Local ethical and regulatory approvals were adhered to. Clinical data were entered to a central, secure database. Accepted cases on the basis of completeness of clinical data were as…
Analysis of extended genomic rearrangements in oncological research.
2007
Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific pathological condition are known. Whole-genome methods are used to discover loci bearing structural abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for the analysis of locus-specific structural changes. The first two a…
Fluorescence In Situ Hybridization (FISH) on Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Sections
2011
Fluorescence In Situ Hybridization (FISH) is a powerful technique for localizing specific DNA targets directly in the fixed tissue or cells. Bacterial artificial chromosome (BAC) as well as commercial probes, which could be supplied ready for use or concentrated and must be diluted following the manufacturers instructions, can be used. The technique requires 2 days, as an overnight incubation of the FISH probes is needed for optimal hybridization. The critical steps include deparaffinization of tissue sections, optimal pretreatment (target retrieval and protein digestion), and probe hybridization. In this chapter, the described FISH protocol provides a methodology for analyzing the cytogene…
Clinical Significance of Rare Copy Number Variations in Epilepsy A Case-Control Survey Using Microarray-Based Comparative Genomic Hybridization
2012
Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = …
Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.
2012
We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele *04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2*04 peaked at 31%. The IGHV1-2*04 rearrangements carried significantly lo…