Ancestry as a potential modifier of gene expression in breast tumors from Colombian women

Abstract

BackgroundHispanic/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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women

“…The results of the current analysis in patients with breast cancer from Peru, and including independent replication in patients from Mexico and Colombia, strongly suggest there could be population-specific genetic variant(s) increasing the risk of HER2 þ tumors among women with IA ancestry. These results are consistent with the previously reported suggestive association between IA ancestry and ERBB2 gene expression (which codes for the HER2 protein) in breast tumors from Colombia (51).…”

Breast Cancer Precision Medicine in Hispanics/Latinas: Focus on Luminal B Tumors

“…These results were confirmed by RT-PCR. In the replication set, the authors found a statistically significant association between ERBB2 expression with IA ancestry (p = 0.02, B = 3.11) [25]. Again, these statistical correlations may reveal biological clues.…”

“…Following up on these intriguing observations, the same group performed wholetranscriptome RNASeq on 21 immunohistochemically defined luminal A and 21 luminal B tumors from the same 301-patient cohort. Serrano-Gomez et al [25] found 67 differentially expressed genes (p < 0.05) from which 39 were upregulated and 28 downregulated in the luminal B subtype (Fig. 13.1).…”

Identification and analysis of small nucleolar RNAs (snoRNAs) associated co-expression and ceRNA regulatory networks in esophageal carcinoma

“…In the ensuing decade, an increasing number of studies have indicated the involvement of snoRNAs in different tumors, including lymphoma, breast cancer, melanoma, and myeloma [8][9][10][11][12]. It has been reported that snoRNAs are regulated in a was complex manner by host genes, copy number variation, and DNA methylation [13].…”