Dataset Information

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

ABSTRACT: BACKGROUND:Molecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations. METHODS:We 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. RESULTS:A 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. CONCLUSIONS:This 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.

SUBMITTER: Liu J

PROVIDER: S-EPMC6833289 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Liu Jiang J Tang Li L Yi Jinhua J Li Guimei G Lu Youwang Y Xu Yu Y Zhao Shuhua S Mao Rui R Li Xiaolu X Ren Li L Wang Kunhua K

BMC gastroenterology 20191105 1

<h4>Background</h4>Molecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations.<h4>Methods</h4>We 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.<h4>Results</h4>A total of 41 cases, 310 cases, and 40 cases were cl ...[more]

PMID: 31690257

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Project description:Background:Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. Patients and methods:The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260?mg/m2 every 3?weeks but was reduced to 220?mg/m2 owing to toxicity. Results:A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2?months compared with 2.1?months, P?=?0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type. Conclusion:Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel therapeutic option for SBA.

Dataset Information

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

Publications

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

Similar Datasets

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