Published in
Public Library of Science, PLoS ONE, 9(7), p. e44997, 2012
DOI: 10.1371/journal.pone.0044997
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An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma
,
Hamoudi Ra,
Naiyan Zeng,
Qingguo Yan,
Yuanxue Huang,
Hongxiang Liu,
Jianzhong Zhang,
Esteban Braggio,
Rafael Fonseca ,
Laurence de Leval ,
Isaacson Pg,
Peter G. Isaacson
and other authors.
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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 (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated 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. These observations provide valuable guidance for further characterisation of 7q deletion.