Array-based DNA methylation profiling in follicular lymphoma.
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.
O'Riain
C
C
Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, Institute of Cancer, London EC1M 6BQ, UK. c.l.oriain@qmul.ac.uk
O'Shea
D M
DM
Yang
Y
Y
Le Dieu
R
R
Gribben
J G
JG
Summers
K
K
Yeboah-Afari
J
J
Bhaw-Rosun
L
L
Fleischmann
C
C
Mein
C A
CA
Crook
T
T
Smith
P
P
Kelly
G
G
Rosenwald
A
A
Ott
G
G
Campo
E
E
Rimsza
L M
LM
Smeland
E B
EB
Chan
W C
WC
Johnson
N
N
Gascoyne
R D
RD
Reimer
S
S
Braziel
R M
RM
Wright
G W
GW
Staudt
L M
LM
Lister
T A
TA
Fitzgibbon
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult