Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: We performed an integrated clinical and genomic analysis of over 7,000 consecutively sequenced colorectal cancer (CRC) samples to comprehensively characterize genetic drivers and metastatic tropisms of CRC. We find that genomic evolutionary changes, such as clonal mutations and oncogenic mutant allelic imbalance, selectively enhance the impact of recurrent oncogenic alterations. We identify the relative timing of organ-specific metastasis, showing sequential metastatic progression in microsatellite stable CRC with brain and adrenal metastases as late events; metastatic sites that cluster together, such as lung, bone, and brain metastases; and genomic events that enhance or decrease risk for each metastatic site, with WNT pathway activation as overall protective while RAS pathway activation increased risk for spread to all metastatic sites. Our data suggest that despite the heterogeneity in CRC, genomic evolution increases the impact of recurrent alterations, and integrating information about tumor primary location and genomics can be used to predict organ-specific metastasis risk.
Source: Cancer Cell
Authors: Paolo Manca, Henry Walch, Jierui Xu, Natalie Small, Ayush Kris, Evan Seffar, Allison Richards, Tiffany Xue, Adam Price, Mark T.A. Donoghue, Christopher Fong, Michele Waters, Justin Jee, Sachin Kumar Deshmukh, George W. Sledge, Midhun Malla, Andrea Cercek, Leonard Saltz, Neil H. Segal, Zsofia K. Stadler, Maliha Nusrat, Michael B. Foote, Avni Desai, Sree Chalasani, Devika Rao, Louise Connell, Richard K.G. Do, Karuna Ganesh, Martin R. Weiser, Michael F. Berger, David B. Solit, Jinru Shia, Efsevia Vakiani, Julio Garcia-Aguilar, Nikolaus Schultz, Francisco Sanchez-Vega, Walid K. Chatila, Rona Yaeger
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Eli Lilly and Company, Pfizer, AstraZeneca, Memorial Sloan-Kettering Cancer Center, Regeneron Pharmaceuticals, Colorectal Cancer Alliance, Mirati Therapeutics, Fund for Innovation in Cancer Informatics, Syndax Pharmaceuticals, Revolution Medicines, National Institutes of Health, Genentech, National Cancer Institute, Daiichi Sankyo Europe
OpenAlex ID: W7204915348