Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 10 April 2020 / Approved: 12 April 2020 / Online: 12 April 2020 (04:22:51 CEST)

A peer-reviewed article of this Preprint also exists.

Davis, M.; Martini, R.; Newman, L.; Elemento, O.; White, J.; Verma, A.; Datta, I.; Adrianto, I.; Chen, Y.; Gardner, K.; Kim, H.-G.; Colomb, W.D.; Eltoum, I.-E.; Frost, A.R.; Grizzle, W.E.; Sboner, A.; Manne, U.; Yates, C. 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. Cancers 2020, 12, 1220. Davis, M.; Martini, R.; Newman, L.; Elemento, O.; White, J.; Verma, A.; Datta, I.; Adrianto, I.; Chen, Y.; Gardner, K.; Kim, H.-G.; Colomb, W.D.; Eltoum, I.-E.; Frost, A.R.; Grizzle, W.E.; Sboner, A.; Manne, U.; Yates, C. 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. Cancers 2020, 12, 1220.

Journal reference: Cancers 2020, 12, 1220
DOI: 10.3390/cancers12051220

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. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 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 2 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.

Subject Areas

triple negative breast cancer; African Ancestry; RNAseq analysis; oncologic pathways

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.