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African Ancestry–Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent

Martini, Rachel; Delpe, Princesca; Chu, Timothy R.; Arora, Kanika; Lord, Brittany; Verma, Akanksha; Bedi, Deepa; Karanam, Balasubramanyam; Elhussin, Isra; Chen, Yalei; Gebregzabher, Endale; Oppong, Joseph K.; Adjei, Ernest K.; Suleiman, Aisha Jibril; Awuah, Baffour; Muleta, Mahteme Bekele.; Abebe, Engida; Kyei, Ishmael; Aitpillah, Frances S.; Adinku, Michael O.; Ankomah, Kwasi; Osei-Bonsu, Ernest Baawuah.; Chitale, Dhananjay A.; Bensenhaver, Jessica M.; Nathanson, David S.; Jackson, Latoya; Petersen, Lindsay F.; Proctor, Erica; Stonaker, Brian; Gyan, Kofi K.; Gibbs, Lee D.; Manojlovic, Zarko; Kittles, Rick A.; White, Jason; Yates, Clayton C.; Manne, Upender; Gardner, Kevin; Mongan, Nigel; Cheng, Esther; Ginter, Paula; Hoda, Syed; Elemento, Olivier; Robine, Nicolas; Sboner, Andrea; Carpten, John D.; Newman, Lisa; Davis, Melissa B.

Authors

Rachel Martini

Princesca Delpe

Timothy R. Chu

Kanika Arora

Brittany Lord

Akanksha Verma

Deepa Bedi

Balasubramanyam Karanam

Isra Elhussin

Yalei Chen

Endale Gebregzabher

Joseph K. Oppong

Ernest K. Adjei

Aisha Jibril Suleiman

Baffour Awuah

Mahteme Bekele. Muleta

Engida Abebe

Ishmael Kyei

Frances S. Aitpillah

Michael O. Adinku

Kwasi Ankomah

Ernest Baawuah. Osei-Bonsu

Dhananjay A. Chitale

Jessica M. Bensenhaver

David S. Nathanson

Latoya Jackson

Lindsay F. Petersen

Erica Proctor

Brian Stonaker

Kofi K. Gyan

Lee D. Gibbs

Zarko Manojlovic

Rick A. Kittles

Jason White

Clayton C. Yates

Upender Manne

Kevin Gardner

Esther Cheng

Paula Ginter

Syed Hoda

Olivier Elemento

Nicolas Robine

Andrea Sboner

John D. Carpten

Lisa Newman

Melissa B. Davis



Abstract

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race–group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an Africanenriched international multiethnic cohort.

Citation

Martini, R., Delpe, P., Chu, T. R., Arora, K., Lord, B., Verma, A., …Davis, M. B. (2022). African Ancestry–Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent. Cancer Discovery, 12(11), 2530-2551. https://doi.org/10.1158/2159-8290.CD-22-0138

Journal Article Type Article
Acceptance Date Aug 23, 2022
Online Publication Date Sep 19, 2022
Publication Date Sep 19, 2022
Deposit Date Sep 24, 2022
Publicly Available Date Sep 20, 2023
Journal Cancer Discovery
Print ISSN 2159-8274
Electronic ISSN 2159-8290
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 12
Issue 11
Pages 2530-2551
DOI https://doi.org/10.1158/2159-8290.CD-22-0138
Keywords Oncology
Public URL https://nottingham-repository.worktribe.com/output/11472714
Publisher URL https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0138/709181/African-Ancestry-Associated-Gene-Expression

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