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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

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Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA
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Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA
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Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA
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Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA
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Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA
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Department of Computational Biology, Weill Cornell Medicine, New York, NY 10065, USA
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Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA
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Department of Pathology and Cell Biology, Columbia University, New York, NY 10027, USA
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Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Department of Hematology and Oncology, Our Lady of Lourdes JD Moncus Cancer Center, Lafayette, LA 70508, USA
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O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10062, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Cancers 2020, 12(5), 1220; https://doi.org/10.3390/cancers12051220
Received: 10 April 2020 / Revised: 7 May 2020 / Accepted: 11 May 2020 / Published: 13 May 2020
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. RNA sequencing data were analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 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 two 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. View Full-Text
Keywords: triple negative breast cancer; African ancestry; RNAseq analysis; oncologic pathways; disparities triple negative breast cancer; African ancestry; RNAseq analysis; oncologic pathways; disparities
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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.

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