Previous studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC) exhibit both recurrent chromosome abnormalities and changes in the expression of numerous genes. However, it is not known to what extent changes in the copy number of individual genes are associated with the observed expression changes. To address this, a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Significant gene expression changes were identified in tumour suppressor genes (TSGs) and in tumour-promoting genes (TPGs) but almost 60% of these can be either upregulated or downregulated in different types of cancer. This suggests that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of onco-suppressors may be more extensive than previously recognised. Several genomic regions showing frequent copy number gain or loss were identified. Whereas TSGs were significantly enriched within regions of frequent loss, no significant enrichment of TPGs was observed in regions of frequent gain. However, on a gene by gene basis little correlation was found between DNA copy number and alterations in gene expression except for loss of expression from homozygous deletions and a single highly amplified segment which showed enhanced gene expression.
A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels.
Disease, Disease stage
View SamplesStudy the training exercise effects in chronic obstructive pulmonary disease (COPD) patients and aged-matched healthy individuals. Skeletal muscle biopsies from 9 stable COPD patients with normal fat free mass index (FFMI, 21Kg/m2) (COPDN), 6 COPD patients with low FFMI (16Kg/m2) (COPL), and 12 healthy sedentary subjects (FFMI 21Kg/m2) before and after 8 weeks of a supervised endurance exercise program were analyzed.
A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.
Specimen part, Disease, Disease stage, Subject
View SamplesWe addressed the clinical significance and mechanisms behind in vitro cellular responses to ionising radiation (IR)-induced DNA double strand breaks in 74 paediatric ALL patients. We found an apoptosis-resistant response in 36% of patients and an apoptosis-sensitive response in the remaining 64% of leukaemias. Global gene expression profiling of 11 apoptosis-resistant and 11 apoptosis-sensitive ALLs revealed abnormal up-regulation of multiple pro-survival pathways in response to IR in apoptosis-resistant leukaemias and differential post-transcriptional activation of the PI3-Akt pathway was observed in representative resistant cases. It is possible that abnormal pro-survival responses to DNA damage provide one of the mechanisms of primary resistance in ALL .
Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.
No sample metadata fields
View SamplesMultiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow in order to survive and proliferate. Interactions between the malignant plasma cell and bone marrow mesenchymal stem cell (BMMSC) are thought to be a critical determinant of this requirement, and include both physical and chemical components. There is increasing evidence that the phenotype of the BMMSC is stably altered in patients with MM. More recently, it has been suggested that this phenotypic transformation is also observed in patients with the benign condition known as monoclonal gammopathy of undetermined significance (MGUS), which almost always precedes MM. In this study, we describe a mechanism by which the peptidyl arginine deiminase 2 (PADI2) enzyme plays an key role in the control of malignant plasma cell phenotype by BMMSCs. PADI enzymes deiminate (citrullinate) peptidyl arginine residues, changing the function or interactions made by the target protein. We identified PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through citrullination of arginine residue 26 of histone H3, it induces the upregulation of interleukin-6 (IL-6) expression. This directly leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.
Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesNasopharyngeal carcinoma (NPC) is a common cancer in southern China and South East Asia where more than 50,000 new cases are diagnosed each year.
The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.
Disease, Disease stage
View SamplesDifferences in chemo-sensitivity of subpopulations of AML stem cells could have important clinical implications. Using in vitro cytotoxicity, xenograft models and colony forming assays, we compared chemotherapy sensitivity between Lineage (Lin-)CD34-CD38-, Lin-CD34-CD38+, Lin-CD34+CD38- and Lin-CD34+CD38+ populations from 26 primary AMLs (19 paediatric and 7 adult). We identified a common recurring pattern of chemo-response associated with a poor clinical outcome: In each of 16/26 (62%) AMLs, Lin-CD34-CD38- cells were the most chemoresistant of the four subpopulations to daunorubicin in vitro. Cytarabine-resistant colonies formed only from Lin-CD34-CD38- populations following tertiary passages through both NOG mice and methylcellulose in these AMLs The presence of chemo-resistant Lin-CD34-CD38- populations was signficantly associated with reduced relapse-free survival in childhood AML. Consistently, CD34 negativity was significantly associated with an increased risk of relapse in a larger retropsective cohort (n=89). Samples enriched for chemo-resistant Lin-CD34-CD38- LSCs with a stem cell profile and an undifferentiated genotype revealed pathways likely to confer chemo-resistance, These strongly indicated dependence of chemo-resistant Lin-CD34-CD38- LSCs on their niche environment as well as deregulated DNA damage responses, lipid and Notch1 signalling, Our findings have major implications for the risk stratification of childhood AML and could lead to the development of novel therapeutic approaches.
No associated publication
Specimen part, Disease, Disease stage, Subject
View SamplesThe Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.
Specimen part, Disease
View Samplescomparison of different ewg isoforms
No associated publication
Age, Time
View SamplesGene expression was compared between four B-cell derived HL cell lines (L428, L1236, L591, KMH2) and GC B cells from three different patients.
The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
No sample metadata fields
View SamplesWhilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.
Cell line
View Samples