Microsatellite instability, <i>MLH1</i> promoter methylation, and <i>BRAF</i> mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel

Vilkin, Alex; Niv, Yaron; Nagasaka, Takeshi; Morgenstern, Sarah; Levi, Zohar; Fireman, Zvi; Fuerst, Florentine; Goel, Ajay; Boland, C. Richard

doi:10.1002/cncr.24019

Cited by 38 publications

(14 citation statements)

References 28 publications

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“…The basic characters of the 61 eligible studies were summarized in Supplementary Table 1 . Thirty-five studies are with sample size below 500 5-37, 64, whereas twenty-six studies are with sample size over 500 38-63. The earliest study was published in July 2005 51, and the latest study was published in August 2017 49.…”

Section: Resultsmentioning

confidence: 99%

“…The earliest study was published in July 2005 51, and the latest study was published in August 2017 49. Most of these studies involved patients with stage I-IV CRC 5, 6, 8, 10, 12, 14, 15, 19, 21, 22, 24, 26, 27, 31, 32, 34, 38, 39, 42, 44-47, 51, 52, 54, 55, 57-60, 64, and six studies only involved patients with stage IV CRC 23, 29, 33, 35, 43, 56. All the studies have a NOS score of ≥5, and 18 studies have a NOS score of ≥6 ( Supplementary Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

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Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Wang¹,

Shen²,

Huang³

et al. 2019

J. Cancer

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Background and Aims: Numerous studies have identified BRAF V600E mutation as a predictive factor of anti-EGFR antibodies in colorectal cancer (CRC). However, the association between BRAF V600E mutation and clinicopathological features remains unclear. Therefore, we aimed to conduct an updated and comprehensive meta-analysis to evaluate the above issues. Methods: We performed a systematic literature search from PubMed, Web of Science, Embase, and PMC database examining the association between BRAF V600E mutation and clinicopathological features in CRC patients. Odds ratio with 95% confidence interval were used to estimate the effects of BRAF V600E mutation on each clinicopathological parameter with fixed-effect model or random-effect model. Results: Sixty-one studies published, including 32407 CRC patients from multiple countries, were included in the meta-analysis. The overall BRAF V600E mutation rate was 11.38%, and BRAF V600E mutation was positively related to high disease stage (OR=0.81; 95% CI=0.72-0.92; P=0.001), high T stage (OR=0.51; 95% CI=0.40-0.65; P<0.00001), proximal colon (OR=4.76; 95% CI=3.81-5.96; P<0.00001) or right colon (OR=5.15; 95% CI=4.35-6.10, P<0.00001) tumor location, poor tumor differentiation (OR=0.27; 95% CI=0.21-0.34; P<0.00001), mucinous histology (OR=2.97; 95% CI=2.37-3.72; P<0.00001), K-ras-wild type (OR=0.04; 95% CI=0.02-0.07; P<0.00001), TP53-wild type (OR=0.50; 95% CI=0.31-0.78; P=0.003), deficient DNA mismatch repair (OR=2.93; 95% CI=1.78-4.82; P<0.00001), high microsatellite instability (OR=11.15; 95% CI=8.51-14.61; P<0.00001) and high CpG island methylator phenotype (OR=0.04; 95% CI=0.03-0.08; P<0.00001). Conclusions: Our updated meta-analysis demonstrated that BRAF V600E mutation was related to poor prognosis of CRC and associated with the distinct molecular phenotypes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Wang¹,

Shen²,

Huang³

et al. 2019

J. Cancer

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“…For tumors with MLH1 protein expression, MLH1 promoter methylation was detected in 11.9% (95% CI: 1.5–53.8%) of the 67 total CRC and in 9.8% (95% CI: 3.4–25.2%) of the 308 sporadic CRC ( P = 0.862; Table 2). Six studies [64], [65], [66], [67], [68], [69] provided expression status as a loss of MLH1 protein expression in 308 cases and MLH1 protein expression in 75 cases of sporadic CRC. The pooled analysis showed significantly association between MLH1 promoter methylation and MLH1 protein expression (OR = 14.919, 95% CI: 6.427–34.631%; P <0.001; I 2 = 35.469%) (Table 3).…”

Section: Resultsmentioning

confidence: 99%

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

Yao

Wang

et al. 2013

PLoS ONE

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PurposeTo describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.MethodsA literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.ResultsThe pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464–3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717–53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; P<0.001) and 9.419 (95% CI: 2.613–33.953; P = 0.001), respectively).ConclusionThe frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.

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“…By contrast, a repressor protein may bind to the A-allele to recruit epigenetic modifying factors leading to promoter methylation and low level of MHL1 transcription [29]. Extensive promoter methylation was associated with MLH1 inactivation [32]. The AA genotype of MLH1 rs1800734 was previously found to be correlated with poor prognosis in Taiwanese patients with lung cancer [27].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of Mismatch Repair Pathway Genes Predict Clinical Outcomes in Oral Squamous Cell Carcinoma Patients Receiving Adjuvant Concurrent Chemoradiotherapy

Senghore

Wang

Chien

et al. 2019

Cancers

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Background: We aimed to investigate the association between single-nucleotide polymorphisms (SNP) in mismatch repair (MMR) pathway genes and survival in patients with oral squamous cell carcinoma (OSCC) who received adjuvant concurrent chemoradiotherapy (CCRT). Methods: Using the Sequenom iPLEX MassARRAY system, five SNPs in four major MMR genes were genotyped in 319 patients with OSCC who received CCRT treatment. Kaplan–Meier survival curves and Cox proportional hazard regression models were used to assess overall survival (OS) and disease-free survival (DFS) among MMR genotypes. Results: The results of Kaplan–Meier survival analysis revealed that the MutS homolog 2 (MSH2) rs3732183 polymorphism showed a borderline significant association with DFS (log-rank p = 0.089). Participants with the MSH2 rs3732183 GG genotype exhibited a relatively low risk of recurrence (hazard ratio (HR) = 0.45; 95% confidence interval (CI) = 0.22–0.96; p = 0.039). In addition, the MutL homolog 1 (MLH1) rs1800734 GG genotype carriers exhibited higher OS (HR = 0.52, 95% CI = 0.27–1.01; p = 0.054) and DFS (HR = 0.49, 95% CI = 0.26–0.92; p = 0.028) rates. Conclusions: Our results indicated that the GG genotypes of MSH2 rs3732183 and MLH1 rs1800734 are associated with relatively high survival in OSCC patients treated using adjuvant CCRT. These polymorphisms may serve as prognosis predictors in OSCC patients.

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Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel

Cited by 38 publications

References 28 publications

Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

Polymorphisms of Mismatch Repair Pathway Genes Predict Clinical Outcomes in Oral Squamous Cell Carcinoma Patients Receiving Adjuvant Concurrent Chemoradiotherapy

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Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel

Cited by 38 publications

References 28 publications

Clinicopathological Significance of BRAFV600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Clinicopathological Significance of BRAFV600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

Polymorphisms of Mismatch Repair Pathway Genes Predict Clinical Outcomes in Oral Squamous Cell Carcinoma Patients Receiving Adjuvant Concurrent Chemoradiotherapy

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Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis