Functional assays for BRCA1 and BRCA2

Abstract

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Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer

“…Two sets of functional assays, including transcriptional activation assay and yeast growth inhibition, are important to provide qualitative evidence. 33 T1691K is confirmed as a deleterious mutation, and S1613G is proved to be a benign polymorphism, consisted with previous observations. Therefore, an effective and robust assessment model is established for the analysis of BRCA1 VUS.…”

“…17 Currently, functional assays are required to characterize the contribution of BRCA1 VUS for breast cancer development, and at least five functional assays have been reported. 33 However, the sensitivity and specificity of the different types of functional assays used to determine the VUS of BRCA1 are variable. 33 It is a difficult and impractical task to perform all of the functional assays, and characterizing all the VUSs identified in patients using the functional assays is not an effective and efficient strategy.…”

“…33 However, the sensitivity and specificity of the different types of functional assays used to determine the VUS of BRCA1 are variable. 33 It is a difficult and impractical task to perform all of the functional assays, and characterizing all the VUSs identified in patients using the functional assays is not an effective and efficient strategy. Therefore, we devised the multimodel assessment using clinical information (pedigree and pathological study) and bioinformatics analysis for pre-screening the VUS, excluding the obvious non-deleterious VUS, and selecting the possible deleterious VUS for further assessment by validated functional assays.…”

“…Functional assay of transcriptional activation is used to evaluate mutations in the Cterminus of BRCA1, and yeast growth inhibition is used for two BRCT domains. 33 For Ring domain, changing the functional analysis to BARD1 binding assay may be a feasible way. 36 Although the currently designed multimodel assessment is limited in the C-terminus of BRCA1, most functionally compromised mutants are located in the C-terminus and Ring domain.…”

Potential Tumor Biomarkers for Ovarian Cancer

“…The BRCA1:BARD1 complex possesses ubiquitin ligase activity (Starita et al, 2004) while the BRCT domains of BRCA1 serve as sites of numerous protein-protein interactions, regulate transcription, and possess the ability to bind to phosphopeptides (reviewed in Narod and Foulkes, 2004;Starita and Parvin, 2003;Manke et al, 2003). Numerous cancer-associated missense mutations which disrupt interactions with putative binding partners have been described in the RING and BRCT domains of BRCA1 (reviewed in Carvalho et al, 2007;Morris and Solomon, 2004;Szabo et al, 2004). The risk of ovarian cancer is about 25% in patients with BRCA2 mutations (Ford et al, 1998).…”