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Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora

Authors: Olopade , Odetunde , Riester , Yoshimatsu , Labrot , Ademola , Saani , Okedere , Mahan , Nwosu , Leary , AJANI Mustapha , Johnson , Sveen , Zheng , Clayton , Khramstova , Oludara , Omodele , Benson , Adeoye A

Publication Type: Conference proceedings

Journal: 305

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Abstract

Objectives: Of all ethnic/racial groups, agestandardized
mortality rate from breast cancer is highest for African American women in the US for
reasons that remain understudied. The paucity of genomic studies of breast tumors across the African Diaspora further restricts our understanding of
the biology of breast cancer in underserved populations. To gain a better understanding of the genomic landscape of breast cancer in women of
African Ancestry, we have developed a cross continent translational research infrastructure to examine the spectrum of genetic alterations in breast
tumors from West Africa compared to the spectrum of alterations observed in tumors from AfricanAmerican
and other women who are
predominantly white in The Cancer Genome Atlas (TCGA) dataset.
Methods: Peripheral blood and breast cancer biopsy tissues were collected from 214 patients enrolled in the West Africa Breast Cancer Study
(WABCS) at the University of Ibadan/University College Hospital (UI/UCH) and at Lagos State University Teaching Hospital (LASUTH). Blood DNA as
well as breast cancer tissue DNA and RNA were extracted at the Novartis Institutes for Biomedical Research (NIBR), UI/UCH, and LASUTH using a
modified protocol of PAXgene Tissue DNA and RNA extraction method. Wholeexome
(WES) and transcriptome (RNAseq)
sequencing were
performed on the Illumina HiSeq2000 platform at NIBR. Single Nucleotide Variants (SNVs) and insertions/deletions (indels) were called using MuTect
and Pindel, while Copy Number Alterations (CNAs) were called using an inhouse
implementation of the ABSOLUTE method. Observed mutations
were compared against those reported in the TCGA dataset. ER, PR and HER2 status were determined by immunohistochemistry (IHC) at UI/UCH,
LASUTH and UChicago.
Results: WES data for 95 tumors have been analyzed thus far. Genes commonly mutated in breast cancer in TCGA are also mutated in WABCS but
the mutational spectrum is vastly different. TP53 (64%), MYC (31%), and GATA3 (26%), showed significantly higher alteration frequencies in WABCS
and African Americans. In contrast, PIK3CA (20%), CDH1 (2%), and MAP3K1 (2%) were less frequently mutated in women of African ancestry. In
addition to the high proportion with TP53 mutations, the proportion with HER2 positive subtype of 42.1% and triplenegative
subtype of 37.9%
suggest that tumors with the most aggressive features are overrepresented in breast cancer patients in West Africa.
Conclusions: In the first study of its kind, high throughput genomic analysis of the largest cohort of women of African ancestry has uncovered
alterations in cancer genes, some of which may be amenable to treatment with targeted therapies. Furthermore, we provide evidence that population
differences in frequency and spectrum of mutations should drive the design and deployment of precision medicine initiatives. Only then can we
develop innovative interventions to reduce the unacceptably high rates of mortality from breast cancer in underserved and under resourced
populations.

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Olopade,O. Odetunde,A. Riester,M. Yoshimatsu,T. Labrot,E. Ademola,A. Saani,A. Okedere,B. Mahan,S. Nwosu,I. Leary,R. AJANI,M. Johnson,R. Sveen,E. Zheng,Y. Clayton,W. Khramstova,G. Oludara,M. Omodele,F. Benson,O. Adeoye,A. . (0000). Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora, 76 (), 1-1.

Olopade,O. Odetunde,A. Riester,M. Yoshimatsu,T. Labrot,E. Ademola,A. Saani,A. Okedere,B. Mahan,S. Nwosu,I. Leary,R. AJANI,M. Johnson,R. Sveen,E. Zheng,Y. Clayton,W. Khramstova,G. Oludara,M. Omodele,F. Benson,O. Adeoye,A. . "Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora" 76, no (), (0000): 1-1.

Olopade,O. and Odetunde,A. and Riester,M. and Yoshimatsu,T. and Labrot,E. and Ademola,A. and Saani,A. and Okedere,B. and Mahan,S. and Nwosu,I. and Leary,R. and AJANI,M. and Johnson,R. and Sveen,E. and Zheng,Y. and Clayton,W. and Khramstova,G. and Oludara,M. and Omodele,F. and Benson,O. and Adeoye,A. and . (0000). Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora, 76 (), pp1-1.

OlopadeO, OdetundeA, RiesterM, YoshimatsuT, LabrotE, AdemolaA, SaaniA, OkedereB, MahanS, NwosuI, LearyR, AJANIM, JohnsonR, SveenE, ZhengY, ClaytonW, KhramstovaG, OludaraM, OmodeleF, BensonO, AdeoyeA, . Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora. 0000, 76 ():1-1.

Olopade,Oi , Odetunde,A , Riester,M , Yoshimatsu,T , Labrot,E , Ademola,A , Saani,A , Okedere,B , Mahan,S , Nwosu,I , Leary,R , AJANI,Mustapha , Johnson,Rs , Sveen,E , Zheng,Y , Clayton,W , Khramstova,G , Oludara,M , Omodele,F , Benson,O , and Adeoye,A . "Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora", 76 . (0000) : 1-1.

O.Oi O.A R.M Y.T L.E A.A S.A O.B M.S N.I L.R A.Mustapha J.Rs S.E Z.Y C.W K.G O.M O.F B.O & A.A , "Abstract P6-03-17: Genomic landscape of breast cancers from women of African ancestry across the diaspora" vol.76, no., pp. 1-1, 0000.

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