Diagnostic accuracy of methods for the detection of BRCA1 and BRCA2 mutations: a systematic review.

摘要: As sequence analysis for BRCA1 and BRCA2 mutations is both time- cost-intensive, current strategies often include scanning techniques to identify fragments containing genetic alterations. However, a systematic assessment of the diagnostic accuracy has been lacking so far. Here, we report on review assess internal external validity techniques. Inclusion criteria were: controlled design, investigators blinded, tests suitable as tool whole genes BRCA2. Outcome parameters were sensitivity, specificity, positive negative predictive values compared direct sequencing. Out 3816 publications, 10 studies reporting 12 methods met our inclusion criteria. The most these was limited. Sensitivities reported be 100% enzymatic mutation detection (EMD), multiple-dye cleavase fragment length polymorphism (MD-CFLP), fluorescence-based conformation-sensitive gel electrophoresis (F-CSGE), RNA-based sequencing, restriction endonuclease fingerprinting-single strand conformation (REF-SSCP), stop codon (SC) assay, denaturing high-performance liquid chromatography (DHPLC). Sensitivity 50-96% SSCP, 88-91% two-dimensional gene (TDGS), 76% (CSGE), 75% protein truncation test (PTT), 58% micronucleus (MNT). Specificities close reported, except MNT. PTT SC assay are only able detect truncating mutations. Most designed introduce new experimental approaches or modifications established require further evaluation. F-CSGE, REF-SSCP, EMD, MD-CFLP will need evaluation before their use in routine setting can considered. MNT, PTT, CSGE, TDGS cannot recommended because low sensitivity. DHPLC outperforms all other studied. none four evaluating performed