CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Takako KawasakiShuji Ogino

Abstract

The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index>4. Low-level methylation (methylation index>0, <20) in each CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (> or =6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (P< or =0.002). In the other six loci (CHFR, HIC1, IGFBP3, MGMT, MINT31 and WRN), which were not highly specific for CIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared...Continue Reading

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Jan 1, 2014·Cancer Metastasis Reviews·Sarah DerksManon van Engeland
Jan 12, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Shuji OginoEdward Giovannucci
Apr 24, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Chee-Seng KuBarry Iacopetta
Jul 23, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Devin C KoestlerAmitabh Srivastava
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