To exploit the rapid advances in high throughput DNA sequencing technologies to realize the goals of precision cancer medicine, we established the Michigan Oncology Sequencing Center (MI-ONCOSEQ). An “integrative sequencing approach” carried out in a CLIA-certified laboratory is utilized to provide a comprehensive landscape of the genetic alterations in individual tumor specimens for the purpose of identifying informative and/or actionable mutations. Using a number of computational pipelines that we have developed in-house or have adapted from the public domain, candidate molecular aberrations are nominated and then analyzed by scientists for clinical significance and or relevance. This approach enables the detection of point mutations, insertions/deletions, gene fusions and rearrangements, amplifications/deletions, and outlier expressed genes. Furthermore, we can identify certain germline alterations that may also be relevant.
Clinical Sequencing Assay
Since the inception of MI-ONCOSEQ in 2011, we collected and evaluated metrics that informed our sequencing and bioinformatic approaches which subsequently resulted in a condensed yet robust sequencing and analytic pipelines with clinically feasible turnaround time. Thus, we transitioned from routine whole-exome sequencing of tumor and normal biospecimen to a targeted panel called OncoSeq that utilizes in solution hybrid-capture methods focusing “sequencing bandwidth” on the protein-coding exons in 1700+ target gene set. The coverage depth is 3X (~ 200X vs. ~ 600X) greater with this approach and can efficiently identify genetic aberrations in both highly recurrent cancer genes as well as a larger additional panel of candidate genes with suggestive links to cancer. Overall, OncoSeq reduced the sequencing and analysis timeframe by ~50%. This lab-developed test is CLIA-certified and results can be utilized to support therapeutic decision-making. Therefore, the OncoSeq assay is used for most routine cases while the whole exome is utilized for specific cases and/or clinical studies.
Click here for technical details of the OncoSeq assay and the 1700+ gene list
Interpretation and Return of Sequencing Results
For all cases that have undergone sequencing and bioinformatic analysis, a molecular report is returned to the treating physician. Treating physicians may share the findings of the comprehensive molecular report with their patients and discuss treatment options as applicable. Select cases of interest and/or with clinically significant findings are presented in a monthly “Precision Medicine Tumor Board” (PMTB) meetings. The multi-disciplinary PMTB, composed of members with expertise in clinical oncology, clinical pathology, cancer genetics, genome biology, bioinformatics, medical genetics and counseling deliberate on the results and potential treatment options. The treating oncologists of patients to be discussed at the PMTB will be informed of the meeting and encouraged to attend.
Physicians, please direct inquiries to our study coordinators at: