Browsing by Author "Falusi, A. G."

Filter results by typing the first few letters
Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    "Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features"
    (Nature Research, 2018) Pitt, J. J.; Riester, M.; Zheng, Y.; Yoshimatsu, T. F.; Sanni, A.; Oluwasola, O.; Veloso, A.; Labrot, E.; Wang, S.; Odetunde, A.; Ademola, A.; Okedere, B.; Mahan, S.; Leary, R.; Macomber, M.; Ajani, M.; Johnson, R. S.; Fitzgerald, D.; Grundstad, A. J.; Tuteja, J. H.; Khramtsova, G.; Zhang, J.; Sveen, E.; Hwang, B.; Clayton, W.; Nkwodimmah, C.; Famooto, B.; Obasi, E.; Aderoju, V.; Oludara, M.; Omodele, F.; Akinyele, O.; Adeoye, A.||; Ogundiran, T.; Babalola, C.; MacIsaac, K.; Popoola, A.; Morrissey, M. P.; Chen, L. S.; Wang, J.; Olopade, C. O.; Falusi, A. G.; Winckler, W.; Haase, K.; Van Loo, P.; Obafunwa, J.; Papoutsakis, D.; Ojengbede, O.; Weber, B.; Ibrahim, N.; White, K. P.; Huo, D.; Olopade, O. I.; Barretina, J
    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.
  • Thumbnail Image
    Item
    Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
    (Nature Research, 2021) Ansari-Pour, N.; Zheng, Y.; Yoshimatsu, T. F.; Sanni, A.; Ajani, M.; Reynier, J.-B.; Tapinos, A.; Pitt, J. J.; Dentro, S.; Woodard, A.; Rajagopal, P. S.; Fitzgerald, D.; Gruber, A. J.; Odetunde, A.; Popoola, A.; Falusi, A. G.; Babalola, C. P.; Ogundiran, T.; Ibrahim, N.; Barretina, J.; Van Loo, P.; Chen, M.; White, K. P.; Ojengbede, O.; Obafunwa, J.; Huo, D.; Wedge, D. C.; Olopade, O. I.
    Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, under scoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.