Dataset Information

Relationship between CpG island methylation phenotype, microsatellite instability phenotype and mutation of KRAS, NRAS, and BRAF genes in colorectal cancer.

ABSTRACT: OBJECTIVE:CpG island methylation phenotype (CIMP) and microsatellite instability (MSI) are two different molecular mechanisms in colorectal cancer (CRC). Proto-oncogene KRAS, mutations in NRAS and BRAF play an important role in the formation of colorectal cancer. The correlation between the molecular typing of CIMP and MSI and the genes of KRAS, NRAS and BRAF was explored in this study. METHODS:A total of 110 paraffin-embedded specimens of colorectal cancer were collected from the Chinese People's Liberation Army Rocket Army Special Medical Center during the period from May 2017 to September 2018. CIMP were detected by DNA methylation quantitative PCR (Methylight). Mutations in KRAS, NRAS, and BRAF genes were detected by realtime fluorescence quantitative PCR (qPCR); MSI typing was detected by sequencing. RESULTS:Of the 110 colorectal cancer samples, 11 cases (10%) were CIMP-H, 92 cases (83.64%) were CIMP-L, and 7 cases (6.36%) were CIMP-0. 10 cases (9.09%) were MSI-H, and 100 cases (90.91%) were MSS and MSI-L. The mutation rates of KRAS, NRAS and BRAF genes were 50% (55 cases), 6.36% (7 cases) and 5.45% (6 cases), respectively. There was no significant correlation between CIMP group and MSI group (P > 0.05). Also, no significant differences were found in the mutations between the three subtypes of the CIMP group and the KRAS, NRAS genes (P > 0.05), while there was a statistically significant difference among the three subtypes of the BR and the BRAF gene mutations (P < 0.0001). There were no obvious differences between the three states of microsatellites and the mutations of KRAS and NRAS genes (P > 0.05), and the differences between them and BRAF gene mutations were statistically significant (P < 0.01). CONCLUSIONS:The BRAF gene mutation is closely related to the two types of CIMP and MSI, which may be an important part of the above two molecular mechanisms, and provide a reference for the treatment of the patients with CIMP-H and MSI-H.

SUBMITTER: Luo Y

PROVIDER: S-EPMC6945156 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Relationship between CpG island methylation phenotype, microsatellite instability phenotype and mutation of KRAS, NRAS, and BRAF genes in colorectal cancer.

Luo Yu Y Cheng Bo B Liu Shan S Xu Lin L Wu Xizhao X Sun Suozhu S

International journal of clinical and experimental pathology 20190301 3

<h4>Objective</h4>CpG island methylation phenotype (CIMP) and microsatellite instability (MSI) are two different molecular mechanisms in colorectal cancer (CRC). Proto-oncogene KRAS, mutations in NRAS and BRAF play an important role in the formation of colorectal cancer. The correlation between the molecular typing of CIMP and MSI and the genes of KRAS, NRAS and BRAF was explored in this study.<h4>Methods</h4>A total of 110 paraffin-embedded specimens of colorectal cancer were collected from the ...[more]

PMID: 31933925

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Project description:The class III histone deacetylase SIRT1 (sir2) is important in epigenetic gene silencing. Inhibition of SIRT1 reactivates silenced genes, suggesting a possible therapeutic approach of targeted reversal of aberrantly silenced genes. In addition, SIRT1 may be involved in the well-known link between obesity, cellular energy balance and cancer. However, a comprehensive study of SIRT1 using human cancer tissue with clinical outcome data is currently lacking, and its prognostic significance is uncertain. Using the database of 485 colorectal cancers in two independent prospective cohort studies, we detected SIRT1 overexpression in 180 (37%) tumors by immunohistochemistry. We examined its relationship to the CpG island methylator phenotype (CIMP), related molecular events, clinical features including body mass index, and patient survival. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1) and eight other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN) by MethyLight. SIRT1 overexpression was associated with CIMP-high (> or =6 of 8 methylated CIMP-specific promoters, P=0.002) and microsatellite instability (MSI)-high phenotype (P<0.0001). In both univariate and multivariate analyses, SIRT1 overexpression was significantly associated with the CIMP-high MSI-high phenotype (multivariate odds ratio, 3.20; 95% confidence interval, 1.35-7.59; P=0.008). In addition, mucinous component (P=0.01), high tumor grade (P=0.02), and fatty acid synthase overexpression (P=0.04) were significantly associated with SIRT positivity in multivariate analysis. SIRT1 was not significantly related with age, sex, tumor location, stage, signet ring cells, cyclooxygenase-2 (COX-2), LINE-1 hypomethylation, KRAS, BRAF, BMI, PIK3CA, HDAC, p53, beta-catenin, COX-2, or patient prognosis. In conclusion, SIRT1 expression is associated with CIMP-high MSI-high colon cancer, suggesting involvement of SIRT1 in gene silencing in this unique tumor subtype.

Dataset Information

Relationship between CpG island methylation phenotype, microsatellite instability phenotype and mutation of KRAS, NRAS, and BRAF genes in colorectal cancer.

Publications

Relationship between CpG island methylation phenotype, microsatellite instability phenotype and mutation of KRAS, NRAS, and BRAF genes in colorectal cancer.

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