Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features
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Jason J Pitt Markus Riester Yonglan Zheng Toshio F Yoshimatsu Ayodele Sanni Olayiwola Oluwasola Artur Veloso Emma Labrot Shengfeng Wang Abayomi Odetunde Adeyinka Ademola Babajide Okedere Scott Mahan Rebecca Leary Maura Macomber Mustapha Ajani Ryan S Johnson Dominic Fitzgerald A Jason Grundstad Jigyasa H Tuteja Galina Khramtsova Jing Zhang Elisabeth Sveen Bryce Hwang Wendy Clayton Chibuzor Nkwodimmah Bisola Famooto Esther Obasi Victor Aderoju Mobolaji Oludara Folusho Omodele Odunayo Akinyele Adewunmi Adeoye Temidayo Ogundiran Chinedum Babalola Kenzie MacIsaac Abiodun Popoola Michael P Morrissey Lin S Chen Jiebiao Wang Christopher O Olopade Adeyinka G Falusi Wendy Winckler Kerstin Haase Peter Van Loo John Obafunwa Dimitris Papoutsakis Oladosu Ojengbede Barbara Weber Nasiru Ibrahim Kevin P White Dezheng Huo Olufunmilayo I Olopade Jordi Barretina Toggle all authors (54)
Abstract
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.
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Journal Nature Communications
Volume 9
Issue number 1
Pages 4181
Available online
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Publisher website (DOI) 10.1038/s41467-018-06616-0
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Europe PubMed Central 30327465
Pubmed 30327465
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