ArticleCancer2009
Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel.
Article in Cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population.BioMed research international · 2022Pooled it
- BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis.PloS one · 2014Pooled it
- MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features.PloS one · 2013Pooled it
- Prevalence of BRAF Mutation in Colorectal Cancer Among Lebanese Patients: A Descriptive Study.Journal of clinical medicine · 2026Article
- Replication-associated mechanisms contribute to an increased CpG > TpG mutation burden in mismatch repair-deficient cancers.Genome medicine · 2025Article
- Microbiota-driven epigenetic modifications in gastrointestinal cancer: Implications for pathogenesis and therapeutic strategies.World journal of microbiology & biotechnology · 2025Review
- Advances in cancer genomics and precision oncology.Genes & genomics · 2025Review
- Article
- Drug discovery in advanced and recurrent endometrial cancer: Recent advances.Oncology research · 2025Review
- Association between colorectal cancer, the frequency of Bacteroides fragilis, and the level of mismatch repair genes expression in the biopsy samples of Iranian patients.BMC gastroenterology · 2024Article
- Multi-omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability.Cancer medicine · 2023Article
- Evolution of Resistance to Irinotecan in Cancer Cells Involves Generation of Topoisomerase-Guided Mutations in Non-Coding Genome That Reduce the Chances of DNA Breaks.International journal of molecular sciences · 2023Article
- Incorporating local ancestry improves identification of ancestry-associated methylation signatures and meQTLs in African Americans.Communications biology · 2022Article
- Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese population with colorectal cancer.BMC gastroenterology · 2019Article
- Article
- Clinicopathological Significance ofJournal of Cancer · 2019Article
- Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel.Familial cancer · 2018Article
- Clinical and Biological Features of Interval Colorectal Cancer.Clinical endoscopy · 2017Review
- KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients.World journal of gastroenterology · 2015Article
- Establishing a biological profile for interval colorectal cancers.Digestive diseases and sciences · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe molecular mechanisms that underlie colorectal cancer (CRC) include microsatellite instability (MSI), chromosomal instability, and the CpG island methylator phenotype. There is evidence to suggest that CRC incidence varies among different ethnic populations worldwide. The authors of this report hypothesized that environmental factors and lifestyle differences among various ethnic groups may differentially influence the epigenetic regulation of tumor suppressor genes in CRC.
methodsIn the current study, microdissection and DNA extraction were performed on 128 samples of CRC from Israeli patients (85 Jews and 43 Arabs). MSI analysis, mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) protein expression levels, and MLH1 promoter methylation were investigated by combined bisulfite restriction analysis. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) valine-to-glutamic acid mutation at residue 600 was investigated by direct DNA sequencing.
resultsHigh MSI (MSI-H), MLH1 methylation, and BRAF mutations were observed in 11.6%, 9.4%, and 23.5% of Jews, respectively, and in 16.2%, 17.6%, and 20.9% of Arabs, respectively (P value nonsignificant). MLH1 promoter methylation was observed in 22.6% of microsatellite-stable (MSS) tumors and in 53.8% of MSI-H tumors (P < .015). Extensive methylation (covering both 5' and 3' promoter regions) was present in all MSI-H tumors with loss of MLH1 expression. BRAF mutation was observed in 15.6% and 46.1% of MSS tumors and MSI-H tumors, respectively (P < .007). BRAF mutation was observed in 66%, 22.2%, and 14.7% of patients who had tumors with extensive MLH1 promoter methylation, methylation of the 5' region alone, or without methylation, respectively (P < .006).
conclusionsThere was no difference in molecular signatures examined between Jewish and Arab patients with CRC in Israel. Extensive promoter methylation was associated with MLH1 inactivation, MSI, and BRAF mutation.
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