Functional identification of non-coding regulatory regions that drive breast and skin carcinogenesis.

Mutations in 12 non-coding regulatory elements are linked to breast and skin cancer development in human and mouse models.

• Why it matters: Understanding non-coding mutations' role in tumorigenesis is limited despite extensive knowledge of protein-coding driver mutations, hindering comprehensive cancer insights.
• What they did: Large-scale functional screens identified these regulatory elements, revealing their association with 16 genes, including MIR21 and ZFP36L2, and demonstrated how their mutation leads to oncogenic transformation.
• The result: Mutating these elements dysregulates gene expression and can drive tumor formation, suggesting non-coding driver mutations are more common and impactful than previously thought.