Characterization of the molecular and clinical features of Multilocus Inherited Neoplasia Allelic Syndrome (MINAS) cases in the Turkish population.

Abstract

Multilocus Inherited Neoplasia Allelic Syndrome (MINAS) is a rare genetic syndrome characterized by the presence of multiple pathogenic/likely pathogenic(P/LP) variants in different cancer predisposition genes within the same individual. Patients with MINAS may face early age at onset and multiple primary malignancies. In our study, we aimed to characterize the prevalence and clinical landscape of MINAS in a major Turkish hereditary cancer cohort. We retrospectively analyzed NGS oncorisk panel results of 5000 individuals who presented to the Medical Genetics Unit of İzmir City Hospital between 2024 and 2025 with a preliminary diagnosis of hereditary cancer syndrome due to a personal and/or family history of malignancy. Our diagnostic workflow uniquely integrated Single Nucleotide Variant (SNV) detection with Copy Number Variation (CNV) calling. MINAS prevalence was 0.86% (43/5000). Dual-gene alterations were detected in 42 patients, while one featured a triple-gene alteration (BRIP1-CHEK2-MUTYH). The most frequent combination was BRCA2-CHEK2 (n = 6). Notably, CNVs were identified in 7% of cases, highlighting the necessity of structural variant analysis. Malignancy was present in 70% (30/43) of carriers, with a median age at first diagnosis of 47 years (range: 31-77). Early-onset cancer (< 40 years) was observed in 32% of cases. Our findings represents the largest Turkish MINAS cohort to date. While phenotypes often align with the most penetrant allele, spesific instances may hint at the potential for synergistic effects in certain individuals. Management should transition toward personalized, multi-variant surveillance strategies incorporating both SNV and CNV data.