The TCGA Legacy

The Cancer Genome Atlas (TCGA) represents a key milestone in the National Cancer Institute’s mission to reduce the burden of cancer suffering. Before TCGA, there was a growing sense in cancer research that we were nearing a complete understanding of the basic biology of cancer. TCGA ended that hubris, identifyingwhole newpathways that were very understudied in cancer biology—for example, the role of the KEAP1-NRF2CUL3 axis in squamous malignancies or the high frequency of SWI/SNF complex subunit mutations in many different types of cancer. I am struck by how an effort that was envisioned as a cataloging of somatic cancer mutations ended up teaching so much basic biology. In retrospect, TCGA was also a critical step toward realizing the promise of precision oncology, providing a ‘‘source code’’ for these efforts to enhance cancer care. Knowing the list of driver mutations in the universe of cancer-causing genetic events allowed for a matching of clinical outcomes with specific mutations. In turn, therapy could be tailored based on those driver mutations, leading to more effective, less toxic cancer treatment. The FDA approval and Centers for Medicare and Medicaid Services coverage of next-generation-sequencing-based tests for patients with advanced cancer marks important additional progress of this effort. Access to these new sequencing technologies for diagnosis and therapy is great news for patients and would not have been possible without the groundwork laid by TCGA. Han Liang TheUniversity of TexasMDAndersonCancer Center