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Cancer Cell2026September 1, 2026Journal Article

Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer.

Paolo Manca1, Henry Walch2, Jierui Xu2, Natalie Small3, Ayush Kris3, Evan Seffar2, Allison Richards4, Tiffany Xue3, Adam Price4, Mark T A Donoghue4, Christopher Fong2, Michele Waters2, Justin Jee5, Sachin Kumar Deshmukh6, George W Sledge6, Midhun Malla7, Andrea Cercek8, Leonard Saltz8, Neil H Segal8, Zsofia K Stadler8, Maliha Nusrat8, Michael B Foote8, Avni Desai8, Sree Chalasani8, Devika Rao8, Louise Connell8, Richard K G Do9, Karuna Ganesh8, Martin R Weiser3, Michael F Berger10, David B Solit11, Jinru Shia12, Efsevia Vakiani12, Julio Garcia-Aguilar13, Nikolaus Schultz2, Francisco Sanchez-Vega14, Walid K Chatila15, Rona Yaeger16
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Oncologia Medica Gastroenterologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
2Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6Caris Life Sciences, Phoenix, AZ, USA.
7University of Alabama, Birmingham, AL, USA.
8Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
9Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
10Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
11Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
12Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
13Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
14Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
15Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: chatilaw@mskcc.org.
16Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: yaegerr@mskcc.org.
PubMed DOI

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 re…

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