Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.
We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.
Schuebel
Kornel E
KE
Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA. kornels@jhmi.edu
Chen
Wei
W
Cope
Leslie
L
Glöckner
Sabine C
SC
Suzuki
Hiromu
H
Yi
Joo-Mi
JM
Chan
Timothy A
TA
Van Neste
Leander
L
Van Criekinge
Wim
W
van den Bosch
Sandra
S
van Engeland
Manon
M
Ting
Angela H
AH
Jair
Kamwing
K
Yu
Wayne
W
Toyota
Minoru
M
Imai
Kohzoh
K
Ahuja
Nita
N
Herman
James G
JG
Baylin
Stephen B
SB
D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers