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SHR Neuro Cancer Cardio Lipid Metab Microb

Vilkin, A; Niv, Y; Nagasaka, T; Morgenstern, S; Levi, Z; Fireman, Z; Fuerst, F; Goel, A; Boland, CR.
Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel.
Cancer. 2009; 115(4):760-769 Doi: 10.1002/cncr.24019 [OPEN ACCESS]
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Co-authors Med Uni Graz: Moazedi-Fürst Florentine
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Abstract:: BACKGROUND: The 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. METHODS: In 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 (BPAF) valine-to-glutamic acid mutation at residue 600 was investigated by direct DNA sequencing. RESULTS: High MSI (MSI-H), MLH1 methylation, and BPAF 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 MLH7 expression. BPAF 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 MLH7 promoter methylation, methylation of the 5' region alone, or without methylation, respectively (P < .006). CONCLUSIONS: There was no difference in molecular signatures examined between Jewish and Arab patients with CRC in Israel. Extensive promoter methylation was associated with MLH7 inactivation, MSI, and BPAF mutation. Cancer 2009;115:760-9. (C) 2009 American Cancer Society.
Find related publications in this database (using NLM MeSH Indexing): Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism; Aged -; Arabs - genetics; Colorectal Neoplasms - diagnosis Colorectal Neoplasms - ethnology Colorectal Neoplasms - genetics; CpG Islands -; DNA Methylation -; DNA Mutational Analysis -; Female -; Humans -; Immunoenzyme Techniques -; Immunoenzyme Techniques -; Jews - genetics; Male -; Microsatellite Instability -; Mutation - genetics; Nuclear Proteins - genetics Nuclear Proteins - metabolism; Phenotype -; Polymerase Chain Reaction -; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism
Find related publications in this database (Keywords): microsatellite instability; mutL homolog 1; BRAF mutation; colorectal cancer; methylation