Project description:T-cell acute lymphoblastic leukemia (T-ALL) is genetically heterogeneous and can be classified into genetic subclasses based on protein coding gene expression profiles. Thus far, long noncoding RNAs (lncRNAs), representing one of the largest fractions of the human transcriptome, remained unexplored as genetics markers for distinct T-ALL subtypes. Therefore, we here determined, for the first time, lncRNA expression profiles in lymphoblasts of 64 T-ALL patients and identified a robust set of lncRNAs that discriminate previously established genetic subtypes of human T-ALL. Half of these lncRNAs were positively correlated with the expression levels of neighboring protein coding genes located in their immediate vicinity, hinting towards cis-regulatory functions. In addition, gene set enrichment analysis showed that these lncRNA signatures were also recapitulated in human T-ALL cell lines representative for the different genetic subclasses, suggesting that these tumor lines could serve as valuable in vitro cellular model systems for further functional lncRNA studies. Finally, comparison of T-ALL lncRNA signatures with those from stage-specific normal developing human thymocytes revealed multiple ectopically expressed, putative oncogenic lncRNAs. Our data identify lncRNAs novel genetic markers in T-ALL biology and warrant further in depth investigations towards landscaping of their specific role in thymopoiesis and leukemogenesis. Gene expression profiles of 10 different T-ALL cell lines
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is genetically heterogeneous and can be classified into genetic subclasses based on protein coding gene expression profiles. Thus far, long noncoding RNAs (lncRNAs), representing one of the largest fractions of the human transcriptome, remained unexplored as genetics markers for distinct T-ALL subtypes. Therefore, we here determined, for the first time, lncRNA expression profiles in lymphoblasts of 64 T-ALL patients and identified a robust set of lncRNAs that discriminate previously established genetic subtypes of human T-ALL. Half of these lncRNAs were positively correlated with the expression levels of neighboring protein coding genes located in their immediate vicinity, hinting towards cis-regulatory functions. In addition, gene set enrichment analysis showed that these lncRNA signatures were also recapitulated in human T-ALL cell lines representative for the different genetic subclasses, suggesting that these tumor lines could serve as valuable in vitro cellular model systems for further functional lncRNA studies. Finally, comparison of T-ALL lncRNA signatures with those from stage-specific normal developing human thymocytes revealed multiple ectopically expressed, putative oncogenic lncRNAs. Our data identify lncRNAs novel genetic markers in T-ALL biology and warrant further in depth investigations towards landscaping of their specific role in thymopoiesis and leukemogenesis.
Project description:We performed DNA methylation (HELP array) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as "germinal center B cell-like" (GCB) and "activated B cell-like" (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, the supervised analysis using HELP data revealed strikingly different DNA promoter methylation patterns in the two molecular DLBCL subtypes. These data provide epigenetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways. The retrospective study included RNA and DNA extracted from 69 clinical samples. This submission represents the gene expression component of the study.
Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal.
2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging.
3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases.
4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.
Project description:We performed DNA methylation (HELP array) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as "germinal center B cell-like" (GCB) and "activated B cell-like" (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, the supervised analysis using HELP data revealed strikingly different DNA promoter methylation patterns in the two molecular DLBCL subtypes. These data provide epigenetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways.
Project description:Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.