Publications by authors named "Ayodele Sanni"

6 Publications

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Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

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, underscoring 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.
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http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

Custodial deaths seen in the Office of the Chief Medical Examiner, Lagos, Nigeria: An 11-year autopsy study.

Med Sci Law 2021 Oct 31;61(4):286-291. Epub 2021 Mar 31.

Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Nigeria.

Introduction: Deaths in custody are a matter of global concern. However, such information is often missing in developing countries. This study aimed to examine retrospectively the profile, cause and manner of deaths amongst cases of custodial deaths in Lagos State, Nigeria.

Method: An 11-year study (June 2008-June 2019) was done of all autopsy cases of custodial deaths in the Office of the Chief Medical Examiner. Variables including age, sex, offence, place of death, duration in custody prior to death and cause and manner of death were extracted from the records. Results were analysed using frequencies and percentages.

Results: Out of 9894 autopsies over the study period, 45 custodial deaths were identified. Males and females constituted 84.4% and 15.6%, respectively (M:F = 5.4:1). Ages ranged from 20 to 64 years, with a mean age of 37 ± 11.0 years. These deaths were most common in the third decade. Armed robbery and financial crime were the two leading reasons for arrest, while most deaths occurred within 24 hours of arrival in custody. The two leading causes of death were acute cardiac failure from hypertensive heart disease and cranio-cerebral injury from blunt-force trauma.

Conclusion: Deaths in custody need to be properly investigated and particular attention needs to be paid to unlawful deaths if and when they arise.
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http://dx.doi.org/10.1177/00258024211004230DOI Listing
October 2021

Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.

Int J Cancer 2019 12 27;145(12):3321-3333. Epub 2019 Jun 27.

Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL.

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h = 0.575, p = 0.010) and the combined APOBEC signatures (h = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.
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http://dx.doi.org/10.1002/ijc.32498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851589PMC
December 2019

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Nat Commun 2019 01 14;10(1):288. Epub 2019 Jan 14.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.
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http://dx.doi.org/10.1038/s41467-018-07886-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331546PMC
January 2019

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Nat Commun 2018 10 16;9(1):4181. Epub 2018 Oct 16.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

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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http://dx.doi.org/10.1038/s41467-018-06616-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191428PMC
October 2018

Inductive and ultrasonic multi-tier interface for low-power, deeply implantable medical devices.

IEEE Trans Biomed Circuits Syst 2012 Aug;6(4):297-308

Electrical and Electronic Engineering Department, Centre for Bio-inspired Technology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.

We report the development of a novel multi-tier interface which enables the wireless, noninvasive transfer of sufficient amounts of power as well as the collection and transmission of data from low-power, deeply implantable analog sensors. The interface consists of an inductive coupling subsystem and an ultrasonic subsystem. The designed and experimentally verified inductive subsystem ensures that 5 W of power is transferred across 10 mm of air gap between a single pair of PCB spiral coils with an efficiency of 83% using our prototype CMOS logic gate-based driver circuit. The implemented ultrasonic subsystem, based on ultrasonic PZT ceramic discs driven in their low-frequency, radial/planar-excitation mode, further ensures that 29 μW of power is delivered 70 mm deeper inside a homogenous liquid environment-with no acoustic matching layer employed-with an efficiency of 1%. Overall system power consumption is 2.3 W. The implant is intermittently powered every 800 msec; charging a capacitor which provides sufficient power for a duration of ~ 18 msec; sufficient for an implant μC operating at a frequency of 500 KHz to transmit a nibble (4 bits) of digitized sensed data.
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http://dx.doi.org/10.1109/TBCAS.2011.2175390DOI Listing
August 2012
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