Transcriptomics

Dataset Information

3

An integrated genomic and expression analysis of 7q deletion in SMZL (Illumina Infinium Human Methylation 27 array)


ABSTRACT: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrative transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P <0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. For methylation arrays. Epigenetic methylation analysis was performed using the Infinium Human Methylation 27 array (Illumina, San Diego, California, USA). The array contained 27,568 CpG islands within the proximal promoter regions of transcription start sites of 14,475 RefSeq genes, including 12,883 well annotated genes (NCBI CCDS database: Build 36). The methylation array was carried out in 12 SMZL (6 cases with 7q deletion), 6 follicular lymphomas (FL) and 6 mantle cell lymphomas (MCL) as per the manufacturer’s instructions. Briefly, 2μg genomic DNA extracted from frozen tissues with >70% tumour cells was bisulphite modified using the EZ DNA Methylation Kit (Zymo Research Corporation). Bisulphite modified DNA was then amplified using the MSM master mix (Illumina) and incubated at 37oC for 22 hours. Amplified DNA was then fragmented and hybridised to BeadChips in an Illumina Hybridisation Oven at 48oC for 18 hours. Following hybridisation, single base extension of hybridised DNA using hapten labelled bases was performed. Staining was then developed using immunochemical stains catalysed by the haptens, and the arrays washed. The chips were scanned using the BeadArray™ Reader (Illumina) and the BeadScan™ software (Illumina) using the Infinium Methylation Scan setting. The scanned data was then analysed in GenomeStudio™ (Illumina) using the Methylation analysis module.

ORGANISM(S): Homo Sapiens

DISEASE(S): Follicular Lymphoma,Splenic Marginal Zone Lymphoma,Mantle Cell Lymphoma

SUBMITTER: Ming Q Du   Yuanxue Huang  Peter G Isaacson  Qingguo Yan  Hongxiang Liu  Andrew Wotherspoon  Laurence de Leval  Alan J Watkins  Rifat A Hamoudi  Esteban Braggio  Naiyan Zeng  Ellen D McPhail  Rafael Fonseca  Jianzhong Zhang  Ahmet Dogan 

PROVIDER: E-GEOD-35424 | ArrayExpress | 2012-08-30

SECONDARY ACCESSION(S): GSE35424PRJNA152589

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-35424.README.txt Txt
E-GEOD-35424.additional.1.zip Other
E-GEOD-35424.idf.txt Idf
E-GEOD-35424.processed.1.zip Processed
E-GEOD-35424.sdrf.txt Txt
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