TY - JOUR
T1 - African Ancestry–Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent
AU - Martini, Rachel
AU - Delpe, Princesca
AU - Chu, Timothy R.
AU - Arora, Kanika
AU - Lord, Brittany
AU - Verma, Akanksha
AU - Bedi, Deepa
AU - Karanam, Balasubramanyam
AU - Elhussin, Isra
AU - Chen, Yalei
AU - Gebregzabher, Endale
AU - Oppong, Joseph K.
AU - Adjei, Ernest K.
AU - Suleiman, Aisha Jibril
AU - Awuah, Baffour
AU - Muleta, Mahteme Bekele
AU - Abebe, Engida
AU - Kyei, Ishmael
AU - Aitpillah, Frances S.
AU - Adinku, Michael O.
AU - Ankomah, Kwasi
AU - Osei-Bonsu, Ernest Baawuah
AU - Chitale, Dhananjay A.
AU - Bensenhaver, Jessica M.
AU - Nathanson, David S.
AU - Jackson, Latoya
AU - Petersen, Lindsay F.
AU - Proctor, Erica
AU - Stonaker, Brian
AU - Gyan, Kofi K.
AU - Gibbs, Lee D.
AU - Monojlovic, Zarko
AU - Kittles, Rick A.
AU - White, Jason
AU - Yates, Clayton C.
AU - Manne, Upender
AU - Gardner, Kevin
AU - Mongan, Nigel
AU - Cheng, Esther
AU - Ginter, Paula
AU - Hoda, Syed
AU - Elemento, Olivier
AU - Robine, Nicolas
AU - Sboner, Andrea
AU - Carpten, John D.
AU - Newman, Lisa
AU - Davis, Melissa B.
N1 - Publisher Copyright:
© 2022, American Association for Cancer Research Inc.. All rights reserved.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/2159-8290.CD-22-0138
DO - 10.1158/2159-8290.CD-22-0138
M3 - Article
C2 - 36121736
AN - SCOPUS:85141190237
SN - 2159-8274
VL - 12
SP - 2530
EP - 2551
JO - Cancer discovery
JF - Cancer discovery
IS - 11
ER -