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乳腺癌易感基因1和2（BRCA1和BRCA2）突变为乳腺癌恶化的风险因素之一。自从BRCA被发现以来，其突变一直是活跃的研究领域之一，这两个基因的新突变不断被描述，并且被不同系统进行分类。 2018年10月6日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表墨西哥国立自治大学、国家癌症研究所的研究报告，分析了BRCA1和BRCA2突变的描述和分类现状，探讨了是否存在较多被描述突变类型的趋势以及致病突变的比例。 结果发现，虽然每年都有新的突变被描述，正如目前数据库记录所反映（1272个BRCA1突变、1320个BRCA2突变），但是这些突变如同流星，很少被其他论文再次提及。分类系统存在高度分歧，其共识仍在制定。由于大量可能变异及其对BRCA基因功能的多种作用，大量突变的功能尚未被深入分析，而这是一项非常复杂艰巨的工作。经过个别分析，许多未知意义的变异被发现具有致病性，并且其中许多变异可以破坏涉及DNA损伤修复通路等机制的其他蛋白质相互作用。最新数据表明，寻找突变方式或其组合，将在未来几年更广泛地阐明BRCA所致乳腺癌易感性。 Breast Cancer Res Treat. 2018 Oct 6. BRCA mutations: is everything said? Eduardo López-Urrutia, Victor Salazar-Rojas, Luis Brito-Elías, Misael Coca-González, Jonathan Silva-García, David Sánchez-Marín, Alma D. Campos-Parra, Carlos Pérez-Plasencia. FES-IZTACALA, UNAM, Tlalnepantla, Mexico; Instituto Nacional de Cancerología. Tlalpan, Mexico. BACKGROUND: Mutations in the BRCA1 and BRCA2 genes constitute a risk factor for breast cancer development. BRCA mutation research has been an active field since the discovery of the genes, and new mutations in both genes are constantly described and classified according to several systems. AIM: We intend to provide an overview of the current state of BRCA1 and BRCA2 mutation description and classification. We wanted to know whether there was a trend towards a more frequently described mutation type and what the proportion of pathogenic mutations was. RESULTS: We found that, although new mutations are described each year as reflected in current database records, very few of them are reported in papers. Classification systems are highly heterogeneous and a consensus among them is still under development. Regarding their function, a large number of mutations are yet to be analyzed, a very complex task, due to the great number of possible variations and their diverse effect in the BRCA gene functions. After individual analysis, many variants of unknown significance turn out to be pathogenic, and many can disrupt interactions with other proteins involved in mechanisms such as DNA damage repair pathways. Recent data suggest that looking for mutation patterns or combinations would shed a wider light on BRCA-derived cancer susceptibility in the upcoming years. KEYWORDS: Breast cancer risk BRCA1 BRCA2 Mutation Complex traits DOI: 10.1007/s10549-018-4986-5
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