Toward Pathway-and Pancancer-Guided Interpretation of an Individual’s Cancer Genome
summary
Reference maps from a pan-cancer atlas (11,000 samples, 33 tumor types) place individual tumors by molecular phenotype, flag ~20–25% of cases that cross tissue boundaries, and guide treatment hypotheses; a pediatric sarcoma mapped to neuroblastoma-like tumors with ALK activity and responds to crizotinib plus a JAK–STAT inhibitor. Methods include a paradigm shift score to call functional driver effects from pathway discordance, network reconstruction with tie-dye patient networks to link mutations → TFs → kinases, and proteomic validation of inferred linkers; networks yield candidate combination targets tested in cell lines.
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