摘要
The study by Dos Santos et al marks a significant advancement in understanding the genetics of colorectal polyposis,particularly within the underrepresented Brazilian population.Utilizing whole-exome sequencing in 27 patients with unexplained polyposis,the researchers identified 16 candidate genes in 44.4%of cases-an impressive outcome given strict exclusion criteria.Many identified variants were linked to the Wnt/β-catenin signaling pathway,reinforcing their biological relevance.However,the study underscores key challenges in genomic medicine,especially the gap between gene discovery and clinical application.A substantial proportion of variants(60.1%)were classified as of uncertain sig-nificance,and the absence of functional validation or segregation analysis limits clinical interpretation.Notably,the potential for oligogenic inheritance com-plicates traditional monogenic models of hereditary cancer risk.The study’s focus on a genetically diverse Brazilian cohort emphasizes the need for population-specific genomic resources and interpretation guidelines.Moving forward,func-tional studies,including organoid models,loss-of-heterozygosity analyses,and genotype-phenotype correlations,are essential to validate findings.Clinically,discovering novel candidate genes may inform future screening and testing pro-tocols,though careful consideration is needed to manage uncertain results.Overall,the study represents a critical step in polyposis genetics,highlighting both progress made and the work still required for clinical translation.
