African Ancestry–Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent-Reference-Cited by-同舟云学术

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

Published:2022-09-19 Issue:11 Volume:12 Page:2530-2551
ISSN:2159-8274
Container-title:Cancer Discovery
language:en
Short-container-title:

Author:

Martini Rachel¹²^ORCID,Delpe Princesca³^ORCID,Chu Timothy R.⁴^ORCID,Arora Kanika⁴^ORCID,Lord Brittany¹²^ORCID,Verma Akanksha³^ORCID,Bedi Deepa⁵^ORCID,Karanam Balasubramanyam⁶^ORCID,Elhussin Isra⁷^ORCID,Chen Yalei⁸^ORCID,Gebregzabher Endale⁹^ORCID,Oppong Joseph K.¹⁰^ORCID,Adjei Ernest K.¹¹^ORCID,Jibril Suleiman Aisha¹²,Awuah Baffour¹³^ORCID,Muleta Mahteme Bekele¹⁴^ORCID,Abebe Engida¹⁴^ORCID,Kyei Ishmael¹⁵^ORCID,Aitpillah Frances S.¹⁰¹⁵^ORCID,Adinku Michael O.¹⁵^ORCID,Ankomah Kwasi¹⁶^ORCID,Osei-Bonsu Ernest Baawuah¹³^ORCID,Chitale Dhananjay A.¹⁷^ORCID,Bensenhaver Jessica M.¹⁸^ORCID,Nathanson David S.¹⁸^ORCID,Jackson LaToya⁸^ORCID,Petersen Lindsay F.¹⁸^ORCID,Proctor Erica¹⁸^ORCID,Stonaker Brian¹^ORCID,Gyan Kofi K.¹^ORCID,Gibbs Lee D.¹⁹^ORCID,Monojlovic Zarko¹⁹^ORCID,Kittles Rick A.²⁰^ORCID,White Jason⁶^ORCID,Yates Clayton C.⁷^ORCID,Manne Upender²¹²²^ORCID,Gardner Kevin²³^ORCID,Mongan Nigel²⁴²⁵^ORCID,Cheng Esther²⁶^ORCID,Ginter Paula²⁶^ORCID,Hoda Syed²⁶^ORCID,Elemento Olivier³²⁷^ORCID,Robine Nicolas⁴^ORCID,Sboner Andrea²⁶^ORCID,Carpten John D.¹⁹^ORCID,Newman Lisa¹^ORCID,Davis Melissa B.¹²³⁴⁸^ORCID

Affiliation:

1. 1Department of Surgery, Weill Cornell Medical College, New York, New York.

2. 2Department of Genetics, University of Georgia, Athens, Georgia.

3. 3Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York.

4. 4New York Genome Center, New York, New York.

5. 5Department of Biomedical Sciences, Tuskegee University, Tuskegee, Alabama.

6. 6Department of Biology, Tuskegee University, Tuskegee, Alabama.

7. 7Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.

8. 8Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.

9. 9Department of Biochemistry, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

10. 10Department of Surgery, Komfo Anokye Teaching Hospital, Kumasi, Ghana.

11. 11Department of Pathology, Komfo Anokye Teaching Hospital, Kumasi, Ghana.

12. 12Department of Pathology, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

13. 13Directorate of Oncology, Komfo Anokye Teaching Hospital, Kumasi, Ghana.

14. 14Department of Surgery, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

15. 15Department of Surgery, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

16. 16Directorate of Radiology, Komfo Anokye Teaching Hospital, Kumasi, Ghana.

17. 17Department of Pathology, Henry Ford Health System, Detroit, Michigan.

18. 18Department of Surgery, Henry Ford Health System, Detroit, Michigan.

19. 19Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, California.

20. 20Department of Population Sciences, City of Hope, Duarte, California.

21. 21Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.

22. 22O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.

23. 23Department of Pathology and Cell Biology, Columbia University, New York, New York.

24. 24Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.

25. 25Department of Pharmacology, Weill Cornell Medical College, New York, New York.

26. 26Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.

27. 27Institute of Computational Biomedicine, Weill Cornell Medical College, New York, New York.

Abstract

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 African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483

Funder

Susan G. Komen

National Cancer Institute

National Institute on Minority Health and Health Disparities

U.S. Department of Defense

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology

Link

https://aacrjournals.org/cancerdiscovery/article-pdf/doi/10.1158/2159-8290.CD-22-0138/3207173/cd-22-0138.pdf

Reference59 articles.