Pormoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas
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- Title
- Pormoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas
- Author(s)
- J C Kim; J S Choi; S A Roh; D H Cho; T W Kim; Yong Sung Kim
- Bibliographic Citation
- Annals of Surgical Oncology, vol. 17, no. 7, pp. 1767-1776
- Publication Year
- 2010
- Abstract
- Background. Promoter methylation of colorectal cancerrelated
genes were examined with respect to phenotype and
tumor progression.
Materials and Methods. We assayed promoter methylation
of 11 genes including established CpG island
methylator phenotype (CIMP) markers (MLH1, MINT1,
MINT2, MINT31, p16INK4a, p14ARF, and CACNA1G) and
four genes (COX2, DAPK, MGMT, and APC) frequently
methylated in colorectal cancer in 285 patients with sporadic
colorectal cancer.
Results. CIMP+ tumors were more than two times more
frequent among high-frequency microsatellite instability
tumors (MSI-H) than in tumors without MSI (P B .0001-
.002). COX2 and DAPK methylation were significantly
associated with CIMP+ and MSI. KRAS showed tendency
toward more frequent codon 12-13 mutations identified in
tumors with APC and p16INK4a methylation than in those
with unmethylation (P = .033 and .05, respectively).
Additionally, tumors with synchronous adenoma were
associated with p16INK4a methylation (P = .004). The
p16INK4a methylation was significantly associated with poor
overall and disease-free survival in 131 rectal cancer
patients who underwent curative operation, according to
multivariate analyses (relative risk [RR] = 0.317 and 0.349;
P = .033 and .024, respectively). Specifically, in 175 stage
II and III patients receiving adjuvant-based fluoropyrimidine
chemotherapy, p16INK4a methylation and MINT31
unmethylation showed a significant or tendency toward an
association with recurrence and DFS (P = .007-.032).
Conclusions. The study suggests that specific CIMP
markers, such as p16INK4a and MINT31, should be further
verified as potential epigenetic targets for the design of
efficient chemotherapy regimens. We also identified a
subset of colorectal cancer, possibly comprising APC
methylation-KRAS mutation-p16INK4a methylation.
- ISSN
- 1068-9265
- Publisher
- Springer
- DOI
- http://dx.doi.org/10.1245/s10434-009-0901-y
- Type
- Article
- Appears in Collections:
- 1. Journal Articles > Journal Articles
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