Building an NGS-based platform for clinical cancer care

This presentation was given by Dr Geoff Otto of Foundation Medicine, Inc, at the Association for Molecular Pathology Annual Meeting on November 12, 2014.

Topics covered in this video:
- Cancer is a Disease of the Genome
- Diagnostic Challenges of Clinical Cancer Specimens
- The FoundationOne Assay, a NGS-based solution for solid tumors

Slides:
- Hallmarks of Cancer: Altered Regulation and Function of Multiple Different Cellular Pathways Leads to Cancer
- The Alterations Relevant to an Individual Patients Disease are Unique
- Cancer is a Disease to the Genome
- Therapies targeting the alterations that drive an individuals patient's cancer can yield dramatic results
- Diagnostic challenge: How to deliver comprehensive genomic profile to the clinic
- Molecular profile of a NSCLC Tumor Specimen (2011 case study)
- NCCN Recommended Profiling Requires Multiple Assays for Relevant Genomic Alterations in Only 3 Genes
- Low Sensitivity of Sanger Sequencing Limits Detection of Base Substitutions and Indels in Typical Specimens
- Technology limits accuracy of Traditional Assays for the detection of genomic alterations in tumor samples
- Requirements of an improved clinical cancer Dx Assay
- Technological revolution of Next Generation Sequencing redefines the limits of Molexular Dx
- Hybrid Capture enables utilization of NGS for comprehensive profile of clinical oncology specimens
- Multiple challenges to building a hybrid capture-based assay for comprehensive genomics profile in cancer
- Iterative optimization of hybrid capture enables highly uniform and deep coverage across hundreds of genes
- Deep unique coverage enables highly accurate and reproducible detection of base subs and indels
- High uniform coverage and select introns is required to detect known and novem genomic rearrangements
- Hybrid capture of known introns enables detection of known and novel genomic rearrangements
- Hybrid capture is highly reproducible and has a high dynamic range
- Reproducible and highly uniform coverage enables detection of copy number alterations at low purity
- Delivering a comprehensive genomic profile in a clinical setting requires an integrated end-to-end workflow
- Analytical Validation
- Application of FoundationOne to Clinical Specimens
- FoundationOne for Solid Tumors
- Molecular Profile of the 2011 NSCLC Tumor Specimen: "pan-negative" by Traditional Assays
- FoundationOne detected a Novem KIF5B-RET Fusion
- Genomic profile versus the "conventional" approach
- Paired CT Scans of Patient with TRIM33-RET
- Pan-Negative NSCLC Study
- HER2/ERBB2 Alterations across 27 Tumor Types