Serrano-Gómez Silvia J, Sanabria-Salas María Carolina, Garay Jone, Baddoo Melody C, Hernández-Suarez Gustavo, Mejía Juan Carlos, García Oscar, Miele Lucio, Fejerman Laura, Zabaleta Jovanny
Grupo de investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá D. C, Colombia.
Programa de doctorado en Ciencias Biológicas, Pontificia Universidad Javeriana, Bogotá D. C, Colombia.
PLoS One. 2017 Aug 23;12(8):e0183179. doi: 10.1371/journal.pone.0183179. eCollection 2017.
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.
西班牙裔/拉丁裔人群是一个基因混合的异质群体，具有不同比例的欧洲、美洲原住民和非洲血统。乳腺癌的分子特征在非西班牙裔白人中已有广泛描述，但西班牙裔/拉丁裔女性缺乏相关知识。我们之前报道过，根据2013年圣加仑标准，哥伦比亚女性中最常见的乳腺癌内在亚型是Luminal B型。在本研究中，我们探讨了这些高度混合的女性中Luminal B型肿瘤分子特征的祖先相关差异。
我们对42例来自哥伦比亚女性的Luminal肿瘤（21例Luminal A型和21例Luminal B型）进行了全转录组RNA测序分析。通过一组80个祖先信息标记（AIM）估计遗传血统。我们根据Luminal亚型以及欧洲和美洲原住民血统比例对患者进行分类，并根据指定的祖先群体对Luminal B型肿瘤与Luminal A型肿瘤进行差异表达分析。
我们发现5个基因可能受遗传血统调控：ERBB2（log2倍变化=2.367，校正P值<0.01）、GRB7（log2倍变化=2.327，校正P值<0.01）、GSDMB（log2倍变化=1.723，校正P值<0.01）、MIEN1（log2倍变化=2.195，校正P值<0.01）和ONECUT2（log2倍变化=2.204，校正P值<0.01）。在重复验证组中，我们发现ERBB2表达与美洲原住民血统之间存在统计学显著关联（P = 0.02，B = 3.11）。该关联不受所分析组中HER2+肿瘤分布的影响。
我们的结果表明，西班牙裔/拉丁裔女性的遗传血统可能会改变Luminal肿瘤中ERBB2基因的表达。需要进一步分析来证实这些发现并探索其预后价值。
