A Prospective, Multicenter, Population-Based Study of BRAF Mutational Analysis for Lynch Syndrome Screening
ABSTRACT Mismatch repair (MMR) deficiencies are the hallmark of tumors arising in Lynch syndrome, however, in approximately 15% of sporadic colorectal cancers (CRC) these deficiencies most often are associated with somatic methylation of the MMR gene MLH1. Recently, an oncogenic mutation in the BRAF gene has been involved in sporadic CRC showing MMR deficiencies as a result of MLH1 promoter methylation. The aim of this study was to evaluate the contribution of BRAF V600E mutation analysis in the identification of MSH2/MLH1 gene mutation carriers in newly diagnosed CRC patients.
BRAF V600E mutation was analyzed in CRC patients with MMR deficiencies (microsatellite instability and/or lack of MLH1/MSH2 protein expression) in the EPICOLON population-based study. The effectiveness and efficiency of different strategies were evaluated with respect to the presence of MSH2/MLH1 germline mutations.
MMR deficiencies were detected in 119 of the 1222 CRC patients with tumors showing either microsatellite instability (n = 111) or loss of protein expression (n = 81). BRAF mutation was detected in 22 (18.5%) of the patients. None of the patients with unambiguous germline mutation had BRAF mutation. Regardless of the strategy used to identify MSH2/MLH1 gene carriers, the introduction of BRAF analysis in these patients slightly improves their effectiveness. The introduction of BRAF mutation analysis as a step before germline genetic testing in patients with MMR deficiencies achieved a significant reduction in costs per mutation detected.
Detection of BRAF V600E mutation could simplify and improve the cost effectiveness of genetic testing for hereditary nonpolyposis colorectal cancer, especially in patients whose family history is incomplete or unknown.
Article: [Colorectal cancer].Bulletin du cancer 02/1994; 81 Suppl 1:27s-31s. · 0.64 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This paper presents a new hardware architecture that calculates SAD for variable block-size motion estimation (VBSME). The proposed architecture with a 16×1-PE array, a 4-stage adder tree and two flexible register arrays supports 16×16, 16×8, 8×8, 8×4, 4×8, and 4×4 block's SAD calculation. The architecture can be used in the encoder that supports the enhanced motion estimation with variable block size in the MPEG-4 AVC (advanced video coding) and the emerging H.264 standard. Our design was described in Verilog-HDL and implemented in a Altera FPGA APEX20K with a clock frequency of 120MHz allowing the processing of 29296 16×16 per search area.ASIC, 2003. Proceedings. 5th International Conference on; 11/2003