We lead a collaborative effort at UCSF to perform integrative genomic analysis of advanced pediatric cancer cases. Using both whole genome sequencing (WGS) and RNA sequencing, our goal is to identify novel drivers of relapse and metastasis in pediatric cancer and to develop new tools that can help guide therapy for patients with high-risk disease. To date we have sequenced over 150 pediatric sarcomas using WGS and RNA sequencing. These large datasets are available for analysis by trainees interested in computational analysis of cancer. Key efforts involve not only identification of possible actionable alterations but also the analysis of longituridanal samples and incorporation of advanced genomic tools such as mutational signature analysis and in silico assessment of heterogeneity in the tumor microenvironment. More recently we have begun studies to expand our “bulk” sequencing to performing single cell and spatially resolved sequencing.

The discovery-focused efforts of our laboratory dovetail well with an extensive and well -developed clinical precision cancer medicine program. A key to this program is the UCSF500 sequencing assay, a CLIA certified molecular assay that can identify mutations, fusion and copy number changes in clinical samples. Unlike many commercially available assays, this test explicitly contains the most important alterations that are relevant to pediatric solid tumors. Over 600 pediatric cancer cases have been sequenced at UCSF using this assay with much of this data available externally thrugh our participation in the AACR GENIE consortium. As an internal resource, extensive clinical data extracted from the electronic health record is also available for these cases. This provides an additional invaluable tool for identification of novel cancer drivers in pediatric cancer. Pediatric cancer cases are frequently discussed in a multi-disciplinary molecular tumor board which all trainees are encouraged to attend, providing a “front row” to the clinical application of genomic analysis in clinical care.