Transcriptomics

Dataset Information

10

INTEGRATIVE ONCOGENOMIC AND HIGH-THROUGHPUT SEQUENCING ANALYSES OF THE COMMONLY DELETED REGION IN CHROMOSOME 7q32 IN SPLENIC MARGINAL ZONE LYMPHOMA (SNP data)


ABSTRACT: Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Notably, deletion or uniparental disomy of chromosome 7q were detected in 39% of SMZLs but in only 9 of 170 (5%) mature B-cell lymphomas (p<10-6). The presence of unmutated IgVH genes, genomic complexity, 17p13-P53 deletion and 8q gain including MYC gene, but not 7q deletion, were correlated with shorter overall survival. Extensive mapping analyses narrowed down the commonly deleted region to 2.7 Mb. in 7q32.1-q32.2 from SND1 to COPG2 genes. High-throughput sequencing analysis of the 7q32 deleted segment in SMZL cells did not identify bi-allelic deletions, insertions or clear pathogenic mutations, but detected six single nucleotide changes in IRF5 (n=2), TMEM209 (n=2), CALU (n=1) and ZC3HC1 (n=1). Comparative expression analysis found that IRF5, TMEM209 and CALU genes had down-regulated expression in lymphomas with 7q32 deletion vs. non-deleted tumors. Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased cell proliferation and induced apoptosis. These results indicate that small deletions, insertions and/or point mutations inactivating genes within 7q32 are not common events in SMZL. Further studies are required to evaluate the putative role of IRF5 in SMZL pathogenesis. Affymetrix GeneChip 50k-XbaI and/or 250-NspI/StyI SNP microarrays were performed for 59 SMZL samples and 4 Marginal Zone cell lines according to the manufacturer's directions.

ORGANISM(S): Homo sapiens  

SUBMITTER: Lourdes Osaba   Jose I Martinez-Ferrandis  Felipe Prosper  Masanori Daibata  Martin J Dyer  Jose A Martinez-Climent  Raquel Malumbres  Miguel A Piris  Vicente Fresquet  Xabier Aguirre  David Oscier  Lorena Fontan  Maria Mena  Javier Martinez-Useros  Anton Parker  Esperanza Vizcarra  Manuela Mollejo  Vicente Jose Fresquet  Maria J Calasanz  David Arteta  Susana Catarino  Jesus M Hernandez-Rivas  A Karpas  Eloy F Robles 

PROVIDER: E-GEOD-35329 | ArrayExpress | 2012-07-31

SECONDARY ACCESSION(S): GSE35329PRJNA156077

REPOSITORIES: GEO, ArrayExpress

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Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Deletion or uniparental disomy of chromosome 7q were detected in 42 of 114 (37%) SMZLs but in only nine of 170 (5%) mature B-cell lymphomas (P < 0·00001). The presence of unmutated IGHV, genomic complexity, 17p13-TP53 deletion and 8q-MYC gain, but not 7q deletion, correlated with shorter overall survival of SMZL patients. Mapping studi  ...[more]

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