# Etiology and Genomics of Breast Cancer Progression in Women of African Ancestry

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $553,775

## Abstract

ABSTRACT
Aggressive breast cancer disproportionately affects young women of African Ancestry across the Diaspora,
who continue to die at an excessively higher rate from the disease than any other racial/ethnic group in the US.
Building on our recent findings that women in Nigeria have high prevalence of tumors with homologous
recombination deficiency signature, our goal is to perform in depth genomic analyses using well phenotyped
tumors from Nigeria. We hypothesize that the genomic determinants of breast cancer subtypes are also
molecular drivers of tumor progression and represent targets for interventions to improve clinical outcomes and
close the mortality gap. Specific aims are: (1) Examine whole genomes of well-phenotyped tumor/normal
pairs to identify somatic mutation signatures and subclonal architecture. Mutation signatures connect
cancer mutational processes to both exogenous and endogenous risk factors. Combined with the whole-
genome and whole-exome sequencing (WGS, WES) data from Nigerian breast cancer patients (100 WGS
and 127 WES) and TCGA (84 WGS and 1008 WES), we will infer mutation signatures and conduct life history
analysis to understand sub-clonal architecture of lethal breast cancers (Year 1); (2) Validate the distribution
of somatic mutation signatures and identify risk factors associated with mutation signatures. We will
perform WES of additional 500 tumor/normal pairs to validate diversity of mutation landscape and signatures in
unselected breast cancer cases in Nigeria (Years 1-5). We will validate somatic mutation spectrum and
signatures identified in Aim 1 and compare to data from publicly available datasets including the TCGA, ICGC,
and in collaboration with the Carolina Breast Cancer Study (CBCS). We will examine association between
mutation signatures, germline variants, molecular subtypes and breast cancer survival. By identifying causal
links between genetic and lifestyle/environmental factors that promote aggressive tumor progression, the
proposed studies will have direct pubic health impact on millions of women in the African Diaspora. (3)
Examine tumor heterogeneity and clonal evolution of breast cancers by sequencing multiple regions of
the tumors. Clonal architecture can be described through the clustering of variants with similar cancer cell
fractions, and also by their geographical distribution, resulting in much greater resolution of subclonal
architecture. We will perform multi-region (4 cores per tumor) WGS, RNA-seq and in-depth analysis of 36
tumors (18 HR- and 18 HR+) to describe genomic inter- and intra-patient tumor heterogeneity that may affect
clinical outcomes (Years 1-5). We will examine differential expression levels, somatic fusion genes, and
aberrant splicing patterns and correlate findings with tumor evolution to infer somatic events that drive tumor
progression. This highly innovative research integrating Nigerian breast cancer researchers with the global
research community has the potential ...

## Key facts

- **NIH application ID:** 9999653
- **Project number:** 5R01MD013452-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Dezheng Huo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $553,775
- **Award type:** 5
- **Project period:** 2019-08-20 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999653

## Citation

> US National Institutes of Health, RePORTER application 9999653, Etiology and Genomics of Breast Cancer Progression in Women of African Ancestry (5R01MD013452-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999653. Licensed CC0.

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