Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Dada Oluwaseyi Temilola; Martha Wium; Juliano Paccez; Azola Samkele Salukazana; Solomon O Rotimi; Hasan H Otu; Giuseppina M Carbone; Lisa Kaestner; Stefano Cacciatore; Luiz Fernando Zerbini

doi:10.3390/genes14101884

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Genes (Basel). 2023 Sep 27;14(10):1884. doi: 10.3390/genes14101884.

Affiliations

¹ International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa.
² Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
³ Division of Urology, University of Cape Town, Groote Schuur Hospital, Cape Town 7925, South Africa.
⁴ Biochemistry Department, Covenant University, Ota 112104, Nigeria.
⁵ Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
⁶ Institute of Oncology Research (IOR), Università della Svizzera italiana, 6900 Bellinzona, Switzerland.

Abstract

Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients. We performed whole exome sequencing (WES) of urinary cfDNA. We identified a novel panel of 31 significantly deregulated somatic mutated genes between PCa and benign prostatic hyperplasia (BPH). Additionally, we performed whole-genome sequencing (WGS) on matching PCa and normal prostate tissue in an independent PCa cohort from South Africa. Our results suggest that the mutations are of germline origin as they were also found in the normal prostate tissue. In conclusion, our study contributes to the knowledge of cfDNA as a biomarker for diagnosing PCa in the South African population.

Keywords: SNVs; South Africa; WGS; cfDNA; prostate cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cell-Free Nucleic Acids* / genetics
Humans
Male
Mutation
Prostatic Hyperplasia* / diagnosis
Prostatic Hyperplasia* / genetics
Prostatic Neoplasms* / diagnosis
Prostatic Neoplasms* / genetics
South Africa

Substances

Cell-Free Nucleic Acids
Biomarkers

Grants and funding

This research was funded by the International Centre for Genetic Engineering and Biotechnology (L.Z. and S.C.); ICGEB Arturo Falaschi fellowship (D.O.T.); and South African National research foundation (NRF) Competitive Support for Unrated Researchers: grant number 138106 (M.W.) and 138113 (S.C.). The APC was waived.