Work

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

Year: 2026

Type: article

Abstract: Whole-genome doubling (WGD) occurs frequently in human cancer and influences tumor evolution, metastasis, and treatment response. Here, we integrate bulk, single-cell, and spatial data to dissect the subclonal dynamics of WGD. Single-cell data analysis shows that WGD cells are prevalent even in tumors that are classified as non-WGD (nWGD). WGD subclones actively acquire somatic copy number alterations as they expand, suggesting ongoing evolution. We developed and rigorously validated a gene expression–based method, WAGES, to map WGD cell clonal fraction in bulk tumors. Applying WAGES to nWGD tumors, we reveal genomic correlates including TP53 mutations and chromosomal instability that are consistent with the presence of WGD subclones. Clinically, WAGES scores are strongly correlated with tumor metastatic potential, response to treatments including chemotherapy and immunotherapy, and patient prognosis. These findings reveal widespread WGD subclones in nWGD tumors and demonstrate their substantial impact on cancer evolution and therapeutic outcomes.

Source: Science Advances

DOI: 10.1126/sciadv.aee7939

Authors: Funan He, Mehwish Noureen, Eloise Dray, Myron S. Ignatius, Xiaojing Wang, Siyuan Zheng

Institutions: The University of Texas at San Antonio Health Science Center, Mays Cancer Center at UT Health San Antonio

Language: English

Topic: Cancer Genomics and Diagnostics

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,500