Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese population with colorectal cancer

Abstract

BackgroundMolecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations.MethodsWe investigated the incidence of CIMP, BRAF/KRAS mutation, and microsatellite instability (MSI) in a Chinese population with CRC (n = 401) and analysed associations between CIMP status and clinicopathological and molecular features.ResultsA total of 41 cases, 310 cases, and 40 cases were classified as CIMP-high, CIMP-low, and CIMP-negative, respectively. We detected a significantly low incidence of BRAF mutation in adenomas (2%) and CRC (0.7%), and a relatively low incidence of KRAS mutation (24.9%) compared with that in other populations. We also detected a relatively low incidence of CIMP-high (10.2%), which was significantly associated with younger age (≤49 years of age), female sex, and proximal tumour location.ConclusionsThis study revealed unique characteristics of CIMP in a Chinese population with colorectal cancer. Developing specific CIMP markers based on unique populations or ethnic groups will further help to fully elucidate CIMP pathogenesis.

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico

“…CIMP-H status was markedly lower in PRH (0.9%) compared to the Spanish, Chinese, and U.S. populations (27.4%, 10%, and 17.5%, respectively). In addition, the MSI-H status of PRH was lower than that of the Chinese population (6.1%; p > 0.05) and significantly lower than that of the U.S. cohort (15.4%; p < 0.001) [ 27 , 28 , 29 ].…”

“…Compared to PRH, the Spanish and U.S. populations had a higher proportion of males by 7.3% and a lower proportion of females by 7.3% and 6.7%, respectively, across both genders. PRH had a higher prevalence of BRAF mutations (9.7%) than what was reported among the Spanish (6.2%; p < 0.05), Chinese (0.7%; p < 0.001), and two U.S. cohort studies, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) (14.6%; p > 0.05) [ 27 , 28 , 29 ]. The prevalence of KRAS mutations in PRH (31.9%) was higher than in the Chinese group (24.9%) but lower than in the Spanish (36.9%) and U.S. cohorts (35.9%), although these differences were not statistically significant.…”

“…This result is markedly lower than the reported prevalence of CIMP-high among non-Hispanic Whites (13%), non-Hispanic Blacks (4.5%), and Hispanics (12.3%) [ 45 ]. We compared the prevalence of tumor markers from PRH with that reported for the nationwide and multicenter Spanish EPICOLON I and EPICOLON II projects, a Chinese population study, and the U.S. cohort studies, NHS and HPFS [ 27 , 28 , 29 ]. PRH has a higher prevalence of BRAF mutations than the Spanish and Chinese populations, but a lower prevalence than the U.S. study cohort.…”

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

“…Loss of a functional DNA mismatch repair system (MMR), through mutations of MSH2 , MSH3, or MSH6 , results in a hypermutable phenotype [ 122 ], with MSI tumors often harboring > 1000 mutations. CIMP was first identified by Toyota et al [ 123 ] and described as hypermethylation of CpG surrounding the promoter regions of certain genes in some CRC patients [ 124 , 125 ]. Since then, many more aberrantly methylated CpG islands (CGI) have been found in CRC and added to the CIMP [ 103 ].…”