Personalized oncology through integrative high thoughout sequencing


Individual cancers harbor a set of genetic aberrations that can be informative for identifying rational therapies currently available or in clinical trials. We have implemented a program to explore the practical challenges of applying high-throughput sequencing in clinical oncology. Through the Michigan Center for Translational Pathology at the University of Michigan, we are enrolling patients with advanced or refractory cancer who are eligible for clinical trials. For each patient, we perform whole-genome sequencing of the tumor, targeted whole-exome sequencing of tumor and normal DNA, and transcriptome sequencing (RNA-Seq) of the tumor to identify potentially informative mutations in a clinically relevant time frame of 4 to 6 weeks. With this approach, we have detected several classes of cancer mutations including structural rearrangements, copy number alterations, point mutations, and gene expression alterations. A multidisciplinary Sequencing Tumor Board (STB) deliberates on the clinical interpretation of the sequencing results obtained. We then share this research information with the patient and their physician. If actionable targets are identified, we utilize clinicaltrials.gov to identify potentially relevant agents for the patient. We beleive that integrative high-throughput sequencing of patients with advanced cancer will generate a comprehensive, individual mutational landscape to facilitate biomarker-driven clinical trials in oncology.