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PMID: 19587707 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Array-based DNA methylation profiling in follicular lymphoma.

Leukemia ·Vol. 23 ·No. 10 ·2009-10-00 ·Pages 1858-66

O'Riain C, O'Shea DM, Yang Y, Le Dieu R, Gribben JG, Summers K, Yeboah-Afari J, Bhaw-Rosun L, Fleischmann C, Mein CA, Crook T, Smith P, Kelly G, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Johnson N, Gascoyne RD, Reimer S, Braziel RM, Wright GW, Staudt LM, Lister TA, Fitzgibbon J

Abstract

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.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Child Child, Preschool CpG Islands DNA Methylation Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Lymph Nodes/pathology Lymphoma, Follicular/genetics Middle Aged Oligonucleotide Array Sequence Analysis Young Adult
Authors & Affiliations
27 authors, click to expand affiliations / ORCID
O'Riain C
Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, Institute of Cancer, London EC1M 6BQ, UK. [email protected]
O'Shea D M
Yang Y
Le Dieu R
Gribben J G
Summers K
Yeboah-Afari J
Bhaw-Rosun L
Fleischmann C
Mein C A
Crook T
Smith P
Kelly G
Rosenwald A
Ott G
Campo E
Rimsza L M
Smeland E B
Chan W C
Johnson N
Gascoyne R D
Reimer S
Braziel R M
Wright G W
Staudt L M
Lister T A
Fitzgibbon J
References (46)
46 references, click to expand
  1. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing.
    Cell. 2007 Sep 21;130(6):1083-94 PMID: 17825402
  2. Large-scale profiling of archival lymph nodes reveals pervasive remodeling of the follicular lymphoma methylome.
    Cancer Res. 2009 Feb 1;69(3):758-64 PMID: 19155300
  3. Ultradeep bisulfite sequencing analysis of DNA methylation patterns in multiple gene promoters by 454 sequencing.
    Cancer Res. 2007 Sep 15;67(18):8511-8 PMID: 17875690
  4. Gene silencing in cancer in association with promoter hypermethylation.
    N Engl J Med. 2003 Nov 20;349(21):2042-54 PMID: 14627790
  5. High-throughput DNA methylation profiling using universal bead arrays.
    Genome Res. 2006 Mar;16(3):383-93 PMID: 16449502
  6. Epigenetic stem cell signature in cancer.
    Nat Genet. 2007 Feb;39(2):157-8 PMID: 17200673
  7. Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band.
    Nat Genet. 2006 May;38(5):540-9 PMID: 16642018
  8. Decitabine--bedside to bench.
    Crit Rev Oncol Hematol. 2007 Feb;61(2):140-52 PMID: 17023173
  9. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.
    PLoS One. 2007 Dec 12;2(12):e1289 PMID: 18074014
  10. Comprehensive high-throughput arrays for relative methylation (CHARM).
    Genome Res. 2008 May;18(5):780-90 PMID: 18316654
  11. Stem cell chromatin patterns: an instructive mechanism for DNA hypermethylation?
    Cell Cycle. 2007 May 2;6(9):1040-3 PMID: 17457052
  12. Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior.
    Leukemia. 2006 Oct;20(10):1855-62 PMID: 16900213
  13. Evidence for an instructive mechanism of de novo methylation in cancer cells.
    Nat Genet. 2006 Feb;38(2):149-53 PMID: 16444255
  14. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.
    Nucleic Acids Res. 2002 Jan 1;30(1):207-10 PMID: 11752295
  15. Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells.
    Mol Cancer Ther. 2007 Feb;6(2):391-403 PMID: 17272646
  16. DNA hypermethylation of myeloid cells, a novel therapeutic target in MDS and AML.
    Curr Pharm Biotechnol. 2006 Oct;7(5):315-21 PMID: 17076647
  17. DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status.
    Leukemia. 2008 May;22(5):1035-43 PMID: 18288132
  18. DNA methylation signatures within the human brain.
    Am J Hum Genet. 2007 Dec;81(6):1304-15 PMID: 17999367
  19. CIMPle origin for promoter hypermethylation in colorectal cancer?
    Nat Genet. 2006 Jul;38(7):738-40 PMID: 16804535
  20. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients.
    J Clin Oncol. 1997 Apr;15(4):1587-94 PMID: 9193357
  21. The history of cancer epigenetics.
    Nat Rev Cancer. 2004 Feb;4(2):143-53 PMID: 14732866
  22. The natural history of initially untreated low-grade non-Hodgkin's lymphomas.
    N Engl J Med. 1984 Dec 6;311(23):1471-5 PMID: 6548796
  23. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma.
    J Clin Oncol. 2007 Jun 10;25(17):2426-33 PMID: 17485708
  24. Regions of acquired uniparental disomy at diagnosis of follicular lymphoma are associated with both overall survival and risk of transformation.
    Blood. 2009 Mar 5;113(10):2298-301 PMID: 19141865
  25. Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14; 18) in follicular lymphoma.
    Am J Clin Pathol. 1995 Apr;103(4):472-8 PMID: 7726146
  26. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
    N Engl J Med. 2004 Nov 18;351(21):2159-69 PMID: 15548776
  27. Control of developmental regulators by Polycomb in human embryonic stem cells.
    Cell. 2006 Apr 21;125(2):301-13 PMID: 16630818
  28. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing.
    Nat Genet. 2007 Feb;39(2):237-42 PMID: 17211412
  29. Epigenetic cancer therapy makes headway.
    J Natl Cancer Inst. 2006 Oct 18;98(20):1443-4 PMID: 17047192
  30. Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review.
    Mol Cancer. 2006 Oct 06;5:44 PMID: 17026765
  31. Molecular pathways in follicular lymphoma.
    Leukemia. 2007 Jan;21(1):18-29 PMID: 17039231
  32. The epigenomics of cancer.
    Cell. 2007 Feb 23;128(4):683-92 PMID: 17320506
  33. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project.
    Blood. 1997 Jun 1;89(11):3909-18 PMID: 9166827
  34. Differential DNA methylation of gene promoters in small B-cell lymphomas.
    Am J Clin Pathol. 2005 Sep;124(3):430-9 PMID: 16191512
  35. Towards defining the lymphoma methylome.
    Leukemia. 2006 Oct;20(10):1658-60 PMID: 17041636
  36. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.
    Nat Genet. 2007 Feb;39(2):232-6 PMID: 17200670
  37. Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation.
    J Clin Oncol. 1988 May;6(5):919-25 PMID: 3284977
  38. A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.
    Leukemia. 2005 Aug;19(8):1459-65 PMID: 15902285
  39. Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma.
    Leukemia. 2007 Jul;21(7):1514-20 PMID: 17495976
  40. Human embryonic stem cells have a unique epigenetic signature.
    Genome Res. 2006 Sep;16(9):1075-83 PMID: 16899657
  41. DNA methylation analysis by pyrosequencing.
    Nat Protoc. 2007;2(9):2265-75 PMID: 17853883
  42. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling.
    Blood. 2009 Mar 12;113(11):2488-97 PMID: 19075189
  43. Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia.
    Haematologica. 2004 Feb;89(2):154-64 PMID: 15003890
  44. Methylation of polycomb target genes in intestinal cancer is mediated by inflammation.
    Cancer Res. 2008 Dec 15;68(24):10280-9 PMID: 19074896
  45. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer.
    Nat Genet. 2002 Jun;31(2):141-9 PMID: 11992124
  46. An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays.
    Cancer Res. 2004 May 1;64(9):3060-71 PMID: 15126342
Article Info
Journal
Leukemia
Abbr.
Leukemia
ISSN
1476-5551
DOI
10.1038/leu.2009.114
Email
[email protected]
Published
2009-10-00
Epub
2009-00-09
Pages
1858-66
Language
English
Region
England
NLM ID
8704895
PMCID
PMC2762475
Subset
IM
Grants
NCI NIH HHS · U01 CA114778 · United States
Cancer Research UK · A9424 · United Kingdom
Cancer Research UK · A8314 · United Kingdom
NCI NIH HHS · 5 U01 CA114778 · United States
Medical Research Council · United Kingdom
Cancer Research UK · MONG1E9R · United Kingdom
External Links
PubMed source DOI: 10.1038/leu.2009.114 PMC Full Text View journal details
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