Faculty, Staff and Student Publications
Language
English
Publication Date
3-13-2026
Journal
Cell Reports
DOI
10.1016/j.celrep.2026.117098
PMID
41832954
Abstract
Cancer is an evolutionary process characterized by profound intratumor heterogeneity (ITH), which can be quantified using in silico estimates of cancer cell fractions (CCFs) of tumor-specific somatic mutations. We demonstrate a data-driven approach based on CCF distributions to identify 4 robust pan-cancer evolutionary signatures from 4,146 tumors across 17 cancer types in The Cancer Genome Atlas (TCGA). These signatures define a continuum of cancer cell fractions reflecting neutral evolution, clonal expansion, and clonal fixation. Correlating evolutionary signatures with mutational and biological programs reveals that tumors enriched for clonal expansion and fixation are associated with immune evasion and distinct changes in the tumor immune microenvironment. Our analysis reveals a dynamic shift from adaptive to innate immune programs as tumors progress toward clonal fixation and escape immune surveillance, accompanied by the clonal expansion of driver genes modulating tumor-stroma interactions. These evolutionary dynamic subtypes are further associated with clinical outcomes and immunotherapy responses.
Keywords
CP: cancer, CP: genomics, cancer evolution, evolutionary dynamics, intratumor heterogeneity, machine learning, pan-cancer, tumor immune microenvironment
Published Open-Access
yes
Recommended Citation
Yang, Xinyu; Liu, Wei; Macintyre, Geoff; et al., "Pan-Cancer Evolution Signatures Link Clonal Expansion to Dynamic Changes in the Tumor Immune Microenvironment" (2026). Faculty, Staff and Student Publications. 6606.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6606
Graphical Abstract
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons