Identification of Distinct Heterogenic Subtypes and Molecular Signatures Associated with African Ancestry in Triple Negative Breast Cancer Using Quantified Genetic Ancestry Models in Admixed Race Populations
Abstract
Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n = 42) and European American (EA, n = 33) women. RNA sequencing data were analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like two tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 13, 2020
- Source ID
- 10.3390/cancers12051220
Entities
People
- Akanksha Verma
- Andra R. Frost
- Andrea Sboner
- Clayton Yates
- Hyung-gyoon Kim
- Indra Adrianto
- Indrani Datta
- Isam-eldin Eltoum
- Jason C White
- Kevin H. Gardner
- Lisa Newman
- Melissa Davis
- Olivier Elemento
- Rachel Martini
- Upender Manne
- William E. Grizzle
- Windy D. Colomb
- Yalei Chen
Organizations
- National Cancer Institute
- National Institute on Minority Health and Health Disparities
- United States Department of Defense