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báo cáo khoa học: "Detection of DNA mismatch repair proteins in fresh human blood lymphocytes - towards a novel method for hereditary non-polyposis colorectal cancer (Lynch syndrome) screening"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Detection of DNA mismatch repair proteins in fresh human blood lymphocytes - towards a novel method for hereditary non-polyposis colorectal cancer (Lynch syndrome) screening | Hassen et al. Journal of Experimental Clinical Cancer Research 2011 30 100 http www.jeccr.eom content 30 1 100 Journal of Experimental Clinical Cancer Research RESEARCH Open Access Detection of DNA mismatch repair proteins in fresh human blood lymphocytes - towards a novel method for hereditary non-polyposis colorectal cancer Lynch syndrome screening 1.2 3 1.2 3 3 3 Samar Hassen 1 Bruce M Boman Nawab Ali 1 Marcie Parker Chandra Somerman Zohra J Ali-Khan Catts Akhtar A Ali1 2t and Jeremy Z Fields1 Abstract Background A broad population-based assay to detect individuals with Lynch Syndrome LS before they develop cancer would save lives and healthcare dollars via cancer prevention. LS is caused by a germline mutation in a DNA mismatch repair MMR gene especially protein truncation-causing mutations involving MSH2 or MLH1. We showed that immortalized lymphocytes from LS patients have reduced levels of full-length MLH1 or MSH2 proteins. Thus it may be feasible to identify LS patients in a broad population-based assay by detecting reduced levels of MMR proteins in lymphocytes. Methods Accordingly we determined whether MSH2 and MLH1 proteins can also be detected in fresh lymphocytes. A quantitative western blot assay was developed using two commercially available monoclonal antibodies that we showed are specific for detecting full-length MLH1 or MSH2. To directly determine the ratio of the levels of these MMR proteins we used both antibodies in a multiplex-type western blot. Results MLH1 and MSH2 levels were often not detectable in fresh lymphocytes but were readily detectable if fresh lymphocytes were first stimulated with PHA. In fresh lymphocytes from normal controls the MMR ratio was 1.0. In fresh lymphocytes from patients N 50 at elevated risk for LS there was a bimodal distribution of MMR ratios range 0.3-1.0 . Conclusions Finding that MMR protein levels can be measured in fresh lymphocytes and given that cells with heterozygote MMR mutations have reduced levels of .