Evidence of active whole-genome doubling (WGD) subclones in non-WGD tumors.

WGD subclones are prevalent and actively evolving in tumors classified as non-WGD (nWGD), acquiring somatic copy number alterations as they expand.

• Why it matters: WGD shapes cancer evolution and treatment response, but subclonal WGD dynamics within nWGD tumors are not well resolved.
• What they did: The study integrates bulk, single-cell, and spatial data, and introduces WAGES, a gene expression-based method, to estimate WGD cell clonal fraction in bulk tumors.
• The result: WAGES applied to nWGD tumors links WGD subclone presence to TP53 mutations and chromosomal instability, and its scores correlate with metastatic potential, treatment response, and patient prognosis.

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