Next-Generation Sequencing Panel for Hereditary Cancer Syndromes: Pilot Implementation in Tertiary Hospitals in Lagos

Hereditary cancer syndromes, caused by germline mutations in cancer predisposition genes, account for five to ten percent of all cancers and carry high lifetime risk for multiple malignancy types. Next-generation sequencing (NGS) multi-gene panels enable simultaneous screening of numerous cancer genes in a cost-effective and efficient manner. This study piloted an NGS hereditary cancer gene panel in oncology patients at two tertiary hospitals in Lagos State, South West Nigeria. One hundred patients with personal and family histories suggestive of hereditary cancer were recruited from oncology units at Lagos University Teaching Hospital and Lagos Island General Hospital. A custom 25-gene panel including BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, PALB2, ATM, CHEK2, and additional genes was sequenced on the Illumina MiSeq platform. Variant classification followed ACMG/AMP guidelines. Pathogenic or likely pathogenic variants were identified in 18 percent of patients. BRCA1 and BRCA2 variants predominated, with several novel Nigerian-specific variants detected. Variants of uncertain significance represented 22 percent of findings, highlighting interpretation challenges in an understudied population. This pilot establishes the clinical feasibility and yield of NGS hereditary cancer panels in Nigerian tertiary oncology settings. Keywords: hereditary cancer, NGS panel, BRCA1, BRCA2, Lagos