Temporal Mapping of Tumor Development in Mice Reveals Late Onset and Benefits of Heterozygosity

Despite decades of cancer research, the stage of life at which cancerous processes lead to tumor formation in various organs remains poorly understood. This uncertainty largely stems from the lack of systematic monitoring of organs across different life stages, resulting in tumors often being detected at various stages of development and making it difficult to determine when they initially emerged and began to grow. Moreover, individuals in real-world settings are exposed to diverse environmental factors that generate substantial inter-individual variability, as lifestyle undeniably contributes to tumorigenesis. To address this gap, we performed regular histological monitoring of tumoral processes in wild-derived laboratory strain mice maintained under standardized laboratory conditions. We specifically compared three small endocrine organs (ovary, thyroid, and adrenal glands) with four larger organs (lung, liver, mammary gland, and kidney) at different time points across the animals' lifespan. To introduce realistic genetic variability, we initially crossed wild-derived inbred laboratory strains. Our findings reveal that the earliest signs of tumor development do not appear before 18 months of age, which is relatively late in the lifespan of these outbred individuals. These results support the view that cancerous processes predominantly emerge in late life and suggest that heterozygosity provides a protective effect, while emphasizing that tumor development remains shaped by interactions with the tissue microenvironment even under controlled conditions.