Array-based DNA methylation profiling in follicular lymphoma

被引：58

作者：

O'Riain, C. ^{[1
]}

O'Shea, D. M. ^{[1
]}

Yang, Y. ^{[1
]}

Le Dieu, R. ^{[1
]}

Gribben, J. G. ^{[1
]}

Summers, K. ^{[1
]}

Yeboah-Afari, J. ^{[2
]}

Bhaw-Rosun, L. ^{[2
]}

Fleischmann, C. ^{[2
]}

Mein, C. A. ^{[2
]}

Crook, T. ^{[3
]}

Smith, P. ^{[3
]}

Kelly, G. ^{[4
]}

Rosenwald, A. ^{[5
]}

Ott, G. ^{[5
,6
]}

Campo, E. ^{[7
]}

Rimsza, L. M. ^{[8
]}

Smeland, E. B. ^{[9
,10
]}

Chan, W. C. ^{[11
]}

Johnson, N. ^{[12
]}

Gascoyne, R. D. ^{[12
]}

Reimer, S. ^{[13
]}

Braziel, R. M. ^{[13
]}

Wright, G. W. ^{[14
]}

Staudt, L. M. ^{[14
]}

Lister, T. A. ^{[1
]}

Fitzgibbon, J. ^{[1
]}

机构：

[1] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Inst Canc, London EC1M 6BQ, England

[2] Barts & London Queen Marys Sch Med & Dent, Genome Ctr, London, England

[3] Inst Canc Res, London SW3 6JB, England

[4] Lincolns Inn Fields, Macrophage Lab, Lincolns Inn Fields, Canc Res UK, London WC2A 3PX, England

[5] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany

[6] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[7] Univ Barcelona, Dept Pathol, Hosp Clin, Barcelona, Spain

[8] Univ Arizona, Ctr Canc, Dept Pathol, Tucson, AZ USA

[9] Univ Hosp, Rikshosp, Inst Canc Res, Dept Immunol, Oslo, Norway

[10] Univ Oslo, Norwegian Radium Hosp, Ctr Canc Biomed, Fac Div, Oslo, Norway

[11] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA

[12] British Columbia Canc Res Ctr, Dept Pathol, Vancouver, BC V5Z 1L3, Canada

[13] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA

[14] NCI, Metab Branch, Bethesda, MD 20892 USA

来源：

LEUKEMIA | 2009年 / 23卷 / 10期

基金：

英国医学研究理事会;

关键词：

methylation; follicular lymphoma; gene expression; polycomb; transformation; B-CELL LYMPHOMA; NON-HODGKINS LYMPHOMAS; EMBRYONIC STEM-CELLS; COLORECTAL-CANCER; PROMOTER HYPERMETHYLATION; INSTRUCTIVE MECHANISM; UNIPARENTAL DISOMY; GENE-EXPRESSION; TRANSFORMATION; POLYCOMB;

D O I：

10.1038/leu.2009.114

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated follicular lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B and T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception, based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes that are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly over-represented among hypermethylated genes. Methylation profiles were conserved in sequential FL and t-FL biopsies, suggesting that widespread methylation represents an early event in lymphomagenesis and may not contribute substantially to transformation. A significant (P<0.05) correlation between FL methylation values and reduced gene expression was shown for up to 28% of loci. Methylation changes occurred predominantly in B cells with variability in the amount of non-malignant tissue between samples preventing conclusive correlation with survival. This represents an important caveat in attributing prognostic relevance to methylation and future studies in cancer will optimally require purified tumour populations to address the impact of methylation on clinical outcome. Leukemia (2009) 23, 1858-1866; doi: 10.1038/leu.2009.114; published online 9 July 2009

引用

页码：1858 / 1866

页数：9

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