文章：

使用计算出的血统分析非洲单克隆丙种球蛋白病患者基因组异常的差异

Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

原文发布日期：2018-10-10

DOI: 10.1038/s41408-018-0132-1

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

摘要翻译： 

多发性骨髓瘤在非裔美国人中的发病率是欧裔美国人的2至3倍。这种显著的差异（在所有癌症中差异程度最高）可能源于群体间潜在的遗传易感性。多发性骨髓瘤存在多种独特的细胞遗传学亚型，而这种差异很可能仅与特定亚型相关。以往理解该差异的研究依赖于自我报告的种族而非遗传血统，这可能产生偏差。为克服这些困难，我们研究了881例接受过统一检测以识别原发性细胞遗传学异常的单克隆丙种球蛋白病患者。我们对骨髓样本DNA进行了精准医学研究芯片基因分型，并使用地理群体结构起源工具定量评估生物地理血统。与非洲血统最低（<0.1%）的235例患者相比，非洲血统最高（≥80%）的120例患者罹患三种特定亚型（即t(11;14)、t(14;16)或t(14;20)）的概率显著更高（分别为51% vs. 33%，p=0.008）。通过定量测量的非洲血统数据，我们证实多发性骨髓瘤的种族差异主要源于t(11;14)、t(14;16)和t(14;20)亚型发生率的差异性分布。

原文链接：

Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry