An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma

A. James Watkins; Rifat A. Hamoudi; Naiyan Zeng; Qingguo Yan; Yuanxue Huang; Hongxiang Liu; Jianzhong Zhang; Esteban Braggio; Rafael Fonseca; Laurence de Leval; Peter G. Isaacson; Andrew Wotherspoon; Ellen D. McPhail; Ahmet Dogan; Ming Qing Du

doi:10.1371/journal.pone.0044997

An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma

A. James Watkins, Rifat A. Hamoudi, Naiyan Zeng, Qingguo Yan, Yuanxue Huang, Hongxiang Liu, Jianzhong Zhang, Esteban Braggio, Rafael Fonseca, Laurence de Leval, Peter G. Isaacson, Andrew Wotherspoon, Ellen D. McPhail, Ahmet Dogan, Ming Qing Du

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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.

Original language	English (US)
Article number	e44997
Journal	PloS one
Volume	7
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0044997
State	Published - Sep 13 2012

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences
General

Access to Document

10.1371/journal.pone.0044997

Cite this

Watkins, A. J., Hamoudi, R. A., Zeng, N., Yan, Q., Huang, Y., Liu, H., Zhang, J., Braggio, E., Fonseca, R., de Leval, L., Isaacson, P. G., Wotherspoon, A., McPhail, E. D., Dogan, A., & Du, M. Q. (2012). An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma. PloS one, 7(9), Article e44997. https://doi.org/10.1371/journal.pone.0044997

@article{f6acf321870c49479d1b91b62c1b4f80,

title = "An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma",

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.",

author = "Watkins, {A. James} and Hamoudi, {Rifat A.} and Naiyan Zeng and Qingguo Yan and Yuanxue Huang and Hongxiang Liu and Jianzhong Zhang and Esteban Braggio and Rafael Fonseca and {de Leval}, Laurence and Isaacson, {Peter G.} and Andrew Wotherspoon and McPhail, {Ellen D.} and Ahmet Dogan and Du, {Ming Qing}",

year = "2012",

month = sep,

day = "13",

doi = "10.1371/journal.pone.0044997",

language = "English (US)",

volume = "7",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma

AU - Watkins, A. James

AU - Hamoudi, Rifat A.

AU - Zeng, Naiyan

AU - Yan, Qingguo

AU - Huang, Yuanxue

AU - Liu, Hongxiang

AU - Zhang, Jianzhong

AU - Braggio, Esteban

AU - Fonseca, Rafael

AU - de Leval, Laurence

AU - Isaacson, Peter G.

AU - Wotherspoon, Andrew

AU - McPhail, Ellen D.

AU - Dogan, Ahmet

AU - Du, Ming Qing

PY - 2012/9/13

Y1 - 2012/9/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84866431776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866431776&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0044997

DO - 10.1371/journal.pone.0044997

M3 - Article

C2 - 23028731

AN - SCOPUS:84866431776

SN - 1932-6203

VL - 7

JO - PloS one

JF - PloS one

IS - 9

M1 - e44997

ER -

An Integrated Genomic and Expression Analysis of 7q Deletion in Splenic Marginal Zone Lymphoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this