Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Differences Between Follicular Lymphoma With and Without Translocation t(14;18)

ABSTRACT: Follicular 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, NFƒÛB, 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. Fresh-frozen tumor-biopsy specimens were obtained from 184 untreated patients who had received a diagnosis of follicular lymphoma. RNA was extracted from the biopsy specimens and was examined for gene expression with the use of Affymetrix U133A and U133B microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Louis Staudt

PROVIDER: E-GEOD-16131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.

Leich Ellen E Salaverria Itziar I Bea Silvia S Zettl Andreas A Wright George G Moreno Victor V Gascoyne Randy D RD Chan Wing-Chung WC Braziel Rita M RM Rimsza Lisa M LM Weisenburger Dennis D DD Delabie Jan J Jaffe Elaine S ES Lister Andrew A Fitzgibbon Jude J Staudt Louis M LM Hartmann Elena M EM Mueller-Hermelink Hans-Konrad HK Campo Elias E Ott German G Rosenwald Andreas A

Blood 20090526 4

Follicular 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 about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridiza ...[more]

PMID: 19471018

Similar Datasets

Project description:The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications. miRNA profiling was performed using Agilent miRNA array platform with RNAs isolated from sorted follicular lymphoma B cells and follicular hyperplasia B cells.

Dataset Information

Differences Between Follicular Lymphoma With and Without Translocation t(14;18)

Publications

Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets