Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.
Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.
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祖先是哥伦比亚妇女乳腺肿瘤中基因表达的潜在修饰剂。
DOI：
10.1371/journal.pone.0183179
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zabaleta J
中科院分区：
文献类型：
--
作者：
Serrano-Gómez SJ;Sanabria-Salas MC;Garay J;Baddoo MC;Hernández-Suarez G;Mejía JC;García O;Miele L;Fejerman L;Zabaleta J
拉美裔/拉丁裔人口是一个基因混杂和异质的群体，有不同比例的欧洲人、美洲土著人和非洲人的祖先。乳腺癌的分子图谱在非西班牙裔白人中得到了广泛的描述，但在西班牙裔/拉丁裔中缺乏同等的知识。我们之前曾报道，哥伦比亚女性中最常见的乳腺癌固有亚型是圣加伦2013年标准定义的Lumina B。在这项研究中，我们探索了这些高度混杂的女性中管腔B肿瘤分子图谱的祖先相关差异。我们对42例来自哥伦比亚妇女的肿瘤(21例A瘤和21例B瘤)进行了全转录基因组RNA-seq分析。遗传祖先是从80个祖先信息标记(AIM)中估计出来的。我们根据管腔亚型和欧洲和美洲土著血统的比例对患者进行分类，并进行差异表达分析，根据分配的祖先组比较管腔B和管腔A肿瘤。我们发现了5个可能受遗传祖先调控的基因：ERBB2(log2FC=2.367，padj<0.01)，grb7(log2fc=2.327，padj<0.01)，GSDMB(log2fc=1.723，padj<0.01，MIEN1(log2FC=2.195，padj<0.01)和ONECUT2(log2FC=2.204，padj<0.01)。在复制集合中，我们发现ERBB2的表达与美洲原住民血统有统计学意义的相关性(p=0.02，B=3.11)。这种关联不受HER2+肿瘤在被分析人群中的分布的影响。我们的结果提示，西班牙裔/拉丁裔女性的遗传祖先可能改变了管腔肿瘤中ERBB2基因的表达。需要进一步的分析来证实这些发现并探索其预后价值。
Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
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