Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort
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Aberrant DNA methylation plays a pivotal role in the onsetand progression of colorectal cancer (CRC), a disease with highincidence and mortality rates in Korea. Several CRC-associateddiagnostic and prognostic methylation markers have been identified;however, due to a lack of comprehensive clinical andmethylome data, these markers have not been validated in theKorean population. Therefore, in this study, we aimed to obtainthe CRC methylation profile using 172 tumors and 128 adjacentnormal colon tissues of Korean patients with CRC. Based onthe comparative methylome analysis, we found that hypermethylatedpositions in the tumor were predominantly concentratedin CpG islands and promoter regions, whereas hypomethylatedpositions were largely found in the open-sea region,notably distant from the CpG islands. In addition, we stratifiedpatients by applying the CpG island methylator phenotype(CIMP) to the tumor methylome data. This stratification validatedprevious clinicopathological implications, as tumors with highCIMP signatures were significantly correlated with the proximalcolon, higher prevalence of microsatellite instability status, andMLH1 promoter methylation. In conclusion, our extensive methylomeanalysis and the accompanying dataset offers valuableinsights into the utilization of CRC-associated methylation markersin Korean patients, potentially improving CRC diagnosis andprognosis. Furthermore, this study serves as a solid foundationfor further investigations into personalized and ethnicity-specificCRC treatments.
Abstract
Aberrant DNA methylation plays a pivotal role in the onsetand progression of colorectal cancer (CRC), a disease with highincidence and mortality rates in Korea. Several CRC-associateddiagnostic and prognostic methylation markers have been identified;however, due to a lack of comprehensive clinical andmethylome data, these markers have not been validated in theKorean population. Therefore, in this study, we aimed to obtainthe CRC methylation profile using 172 tumors and 128 adjacentnormal colon tissues of Korean patients with CRC. Based onthe comparative methylome analysis, we found that hypermethylatedpositions in the tumor were predominantly concentratedin CpG islands and promoter regions, whereas hypomethylatedpositions were largely found in the open-sea region,notably distant from the CpG islands. In addition, we stratifiedpatients by applying the CpG island methylator phenotype(CIMP) to the tumor methylome data. This stratification validatedprevious clinicopathological implications, as tumors with highCIMP signatures were significantly correlated with the proximalcolon, higher prevalence of microsatellite instability status, andMLH1 promoter methylation. In conclusion, our extensive methylomeanalysis and the accompanying dataset offers valuableinsights into the utilization of CRC-associated methylation markersin Korean patients, potentially improving CRC diagnosis andprognosis. Furthermore, this study serves as a solid foundationfor further investigations into personalized and ethnicity-specificCRC treatments.
참고문헌 (37)
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