TRACERx: Trailblazing Longitudinal Cancer Genomics
, by Jean C. Zenklusen, M.S., Ph.D.
Over the past decade, The Cancer Genome Atlas’s (TCGA’s) rich genomic dataset has been analyzed in more than one thousand scientific publications. There is no doubt that TCGA’s analysis of tumor genomes from one biopsy per patient has enabled countless discoveries, but having only a single snapshot of a patient and their cancer limits what we can learn about how cancer evolves and progresses. As I help transition the focus of NCI’s Center for Cancer Genomics (CCG) from TCGA to new explorations of the cancer genome, I am encouraged by the promise of innovative methodologies that go beyond TCGA’s characterization model to address new questions.
Tracking Non-Small-Cell Lung Cancer Evolution through Therapy (TRACERx) is one such innovative cancer study, which I discuss in a new editorial co-written with Ana Robles, Ph.D. TRACERx is a large-scale genomic study by Cancer Research UK, designed by principal investigator Charles Swanton, M.D., Ph.D., to advance the most current model of cancer, which views tumors not as a single entity, but as an ecosystem evolving under selective pressure. TRACERx characterizes non-small-cell lung cancer tissue samples from patients over the course of their treatment: at initial presentation and at each subsequent relapse. This model of tracking tumors over time, combined with sequencing them deeply, enables TRACERx to observe tumor sub-clones as they evolve.
TRACERx’s report on the first 100 enrolled patients demonstrates that its longitudinal design can uncover clinically relevant genomic features. For example, the TRACERx analysis found that the contribution of chromosome instability to heterogeneity within tumors was a better predictor of future patient relapse than the contribution of “driver” gene mutations. This suggests that the current clinical standard of using targeted sequencing panels to identify gene mutations may be improved by the adoption of more advanced methods.
This initial report is only the beginning of TRACERx’s contributions to cancer research, and I am thrilled that CCG’s Cancer Driver Discovery Program will further strengthen the study by providing whole genome sequencing and total RNA sequencing. I anticipate that these platforms will help to paint a clearer picture of tumor evolution and response to therapy and look forward to collaborating on this exciting study.