We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples when compared to normal B cells.
Identification of highly methylated genes across various types of B-cell non-hodgkin lymphoma.
Specimen part, Disease, Disease stage
View SamplesTransformation of follicular lymphoma (FL) to a more aggressive disease is associated with rapid progression and death. Existing molecular markers for transformation are few and their clinical impact is limited. Here, we report on a whole-genome study of DNA copy numbers and gene expression profiles in serial FL biopsies. We identified 698 genes with high correlation between gene expression and copy number and the molecular network most enriched for these cis-associated genes. This network includes 14 cis-associated genes directly related to the NFB pathway. For each of these 14 genes, the correlated NFB target genes were identified and corresponding expression scores defined. The scores for six of the cis-associated NFB pathway genes (BTK, IGBP1, IRAK1, ROCK1, TMED7-TICAM2 and TRIM37) were significantly associated with transformation. The results suggest that genes regulating B-cell survival and activation are involved in transformation of FL
Whole-genome integrative analysis reveals expression signatures predicting transformation in follicular lymphoma.
Specimen part
View SamplesT-cell/histiocyte rich B cell lymphoma (THRBL) and nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) share some morphological characteristics, including a prominent stromal reaction, but display a markedly different prognosis. To investigate the difference between the stromal reactions of these lymphomas at the molecular level, we performed microarray expression profiling on a series of THRBL and NLPHL cases.
T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response.
Sex, Specimen part
View SamplesDespite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.
Disease, Disease stage, Subject
View SamplesFollicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
Specimen part, Disease, Disease stage, Subject
View SamplesMolecular signatures to improve diagnosis in PTCL and prognostication in angioimmunoblastic T-cell lymphoma (AITL). Gene expression profiling of PTCL patient samples was performed to investigate whether molecular signatures can be used to identify distinct entities of PTCL.
Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.
Sex, Age, Specimen part
View SamplesThe assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.
Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesWe performed array comparative genomic hybridization (aCGH) and gene expression profiling in 203 samples of diffuse large B cell lymphoma (DLBCL). By gene expression, at least three molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal B cell lymphoma (PMBL) can be distinguished. Combining gene expression profiling and aCGH, revealed copy number abnormalities that had strikingly different frequencies in the three molecular DLBCL subtypes. These data provide genetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways.
Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesNK-cell lymphoma shares strikingly similar molecular features with a distinct subset of gamma-delta T-cell lymphoma. Gene expression profiling of NK-cell lymphoma patient samples was performed to investigate whether molecular signatures can be used to identify entities of peripheral T-cell lymphoma (PTCL) with NK-cell-like features.
Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro.
Sex, Age, Specimen part
View Samples