Project description:Genome wide DNA methylation profiling of 26 primary central nervous system lymphomas (PCNSL). The Illumina Infinium HumanMethylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in PCNSL samples.
Project description:This SuperSeries is composed of the following subset Series: GSE25297: Genome-wide gene expression comparison (primary central nervous system lymphoma (PCNSL) vs normal lymph node) GSE25298: Genomic aberrations in primary central nervous system lymphoma (PCNSL) Refer to individual Series
Project description:Primary lymphomas of the central nervous system (PCNSL) are diffuse large B-cell lymphomas (DLBCLs) which are confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the mutational landscape in PCNSL, we here performed integrative whole genome and transcriptome sequencing analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL.
Project description:Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a “CNS signature.” Keywords: disease state analysis
Project description:Purpose: Only a limited number of genetic studies have been performed in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy-number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization in formalin fixed paraffin embedded (FFPE) specimens and compare the results with matched frozen tumor specimens. Experimental design: We performed array-based comparative genomic hybridization (aCGH) in FFPE tissues from PCNSL. Results were compared with matched paired frozen tumors. Results: Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes with a median of 23 copy-number abnormalities (CNA) per patient (range 17-47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, 9p21.3 and gain of 12q12-q24.33 were the commonest CNA. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX). Conclusions: The results obtained are encouraging. Larger archival tissue collections can now be analyzed in order to complement the still fragmented knowledge we have of the genetic basis of the PCNSL. We included samples from 7 PCNSL patients. In 6 out of these 7 PCNSL patients (cases B – G), aCGH experiments were performed in DNA samples obtained from both snap-frozen and FFPE tissues for assay quality comparative purposes. In the remaining sample (case A), only frozen sample was analyzed.
Project description:To characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL), 21 PCNSL of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B cell lymphomas (DLBCL), and (iii) to be in part assigned to the activated B cell-like (ABC) or the germinal center B cell-like (GCB) subtype of DLBCL. Experiment Overall Design: Total RNA was extracted from tissue blocks containing > 80% tumor cells using the TRIzol reagent (Invitrogen, Carlsbad, CA) and purified using RNeasy Kit (Qiagen, Valencia, CA). Double-stranded cDNA (ds-cDNA) was generated from 5 μg of total RNA using the SuperScript Double Stranded cDNA Synthesis Kit (Invitrogen) and a poly-dT oligonucleotide that contains T7 RNA polymerase initiation site (Sigma-Proligo, St. Louis, MO). The ds-cDNA was used as template to generate biotinylated cRNA by in vitro transcription using MEGA-script T7 High Yield Transcription Kit (Ambion, Austin, TX), biotin-11-CTP, and biotin-11-UTP (Perkin Elmer, Altham, MA). The biotinylated cRNA was purified by RNAeasy Kit (Qiagen) and fragmented according to the Affymetrix protocol. 15 μg of fragmented cRNA was hybridized to HG-U95Av2 microarrays (Affymetrix, Santa Clara, CA). Gene expression values were determined by GCOS1.2 software (Affymetrix) using the global scaling option.
Project description:A genome-wide gene expression comparison between primary central nervous system lymphoma (PCNSL) and normal lymph node was performed to identify a differential exprssion and specific pathway. Experiment design: 7 PCNSL and 7 normal lymph node tissues were used for comparison.