Massively parallel screen uncovers many rare 3′ UTR variants regulating mRNA abundance of cancer driver genes

Summary

This laboratory study employed high-throughput screening (MapUTR) to characterise the functional impact of rare 3′ UTR variants on mRNA abundance in cancer-relevant genes. Among 17,301 rare variants, 24.5% were functional, with 70% located in cancer-related genes; interrogation of somatic mutations identified 3,928 (33%) functional variants in 155 cancer driver genes. The authors introduce untranslated tumour mutational burden (uTMB) as a potential prognostic metric and experimentally validate cancer-driving potential of three variants (MFN2, FOSL2, IRAK1) through prime editing, suggesting non-coding variants contribute meaningfully to oncogenic gene expression.

Regional applicability

This is a fundamental molecular oncology study with no direct farming, food systems, or nutritional application. The findings are applicable to global cancer genomics and precision oncology regardless of geography, but are out of scope for Vitagri's Pulse Brain focus on agricultural systems, soil health, and food-based nutrition.

Key measures

Functional variant identification (% of rare variants with regulatory effect), enrichment in microRNA- and protein-binding sites, somatic mutation functionality in cancer driver genes, uTMB score, patient survival prediction, mRNA abundance changes from prime editing

Outcomes reported

The study identified functional rare 3′ UTR variants affecting mRNA abundance using high-throughput screening (MapUTR) across 17,301 gnomAD variants and 11,929 somatic mutations in cancer driver genes. The research introduced untranslated tumour mutational burden (uTMB) as a prognostic metric and validated cancer-driving potential of specific variants through prime editing.

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