Abstract Africa has some of the highest age adjusted cancer mortality rates globally and cancer incidence in Africa is expected to double by 2040. Despite this disproportionate burden of disease, African cancer patients are woefully understudied along the cancer continuum. People of African descent are significantly underrepresented in cancer research, accounting for less than 3% of globally available genomic data and are often the least well served by advances in precision medicine.To address this gap, we have initiated the African Cancer Atlas project. This is an Africa-centred approach to overcoming cancer inequities - providing much needed biological and clinical data, but also seeking to identify and address the social determinants of inequities both within the continent and between high and low-middle income countries (LMIC). We have established an oncology partner network across 9 geographically dispersed African countries (Senegal, Côte d’Ivoire, Ghana, Nigeria, Kenya, Uganda, Zimbabwe, South Africa, and Tunisia). We have developed LMIC-specific standardised protocols and best practices for sample collection and processing across multiple sites and continue to build a well-annotated bank of tissue, plasma, bone marrow and PBMC from individuals with breast, prostate, gastrointestinal cancers, liver, urinogenital and pediatric cancers that will be unrivalled in its diversity. So far, 1800 cancer samples have been collected and banked. We have also built a unique cloud-based clinical data management platform to facilitate the collection of longitudinal clinical metadata into a unified clinico-demographic database. We have initiated extensive genomic and molecular profiling of African-specific cancers using whole exome/genome sequencing (WES/WGS) of paired germline and tumour samples as well as RNA- sequencing of tumors. We have so far completed the first 200 WES, representing the first cancer samples sequenced entirely on the African continent. Ongoing work is investigating how population-specific genetic variation contributes to cancer risk, identifying driver mutations, somatic copy number alterations (SCNAs) and mutational signatures that can point to disease-relevant environmental exposures or impaired core biological pathways. Comparative analysis with existing cancer genomics cohorts will determine the prevalence of known hotspot mutations, cancer drivers and or common SCNAs in African cancer genomes. By comparing with available data for African Americans and other diasporan Africans, we will provide better understanding of cancer aetiology related to African ancestry applicable to the broader African diasporic communities in other regions of the world. We are also collecting data to assess socio-economic and health system factors affecting access to cancer care and survival across all study sites. Socio-demographic data collection is integrated with tissue/biodata collection creating digital longitudinal hospital-based cohorts. We will develop systems that integrate genomics, molecular demographics and clinical data with machine learning and a publicly accessible portal for data access and analytics will be available for the broader scientific community. Ultimately, this project will contribute towards better understanding of cancer among people of African descent and make precision oncology more effective for diverse populations. Citation Format: Yaw Bediako, Joyce Ngoi, Ruth Kiome, Seth Agyemang, Stephen Darkoh, Audrey Lemacon, Aida Manu, Frank Onyambu, Kanny Diallo, Lily Paemka, David Hutchful, Emmanuella Amoako, Abdoulaye Diallo. The African Cancer Atlas: Leveraging African data to diversify precision oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB336.