Building a Scalable Clinical Genomics Program - Spring 2021

Explore a comprehensive lecture on building a scalable clinical genomics program for cancer care, risk assessment, and detection. Delve into advanced NGS-based DNA testing techniques, including tumor tissue profiling, clinical interpretation of sequence variants, and automated monitoring for precision oncology. Learn about data sharing paradigms, clinical germline assessment, and the implications of tumor/normal sequencing for cancer risk inference. Examine the prevalence of clonal hematopoiesis and its clinical significance. Investigate the limitations of tissue-based DNA sequencing and the potential of plasma cell-free DNA profiling. Discover cutting-edge approaches to rare variant detection, including ultra-deep sequencing and error suppression techniques. Gain insights into polyclonal acquired resistance in cancer treatment and ongoing efforts to increase sensitivity in detecting circulating tumor DNA. Explore future prospects for clinical sequencing, including the incorporation of more genes, non-coding regions, and viral DNA analysis.

Intro
Comprehensive NGS-Based DNA Testing at MSKCC
MSK-IMPACT for Tumor Tissue Profiling
Clinical Interpretation of Sequence Variants OnceKB
Automated Monitoring for Precision Oncology Clinica
MSK-IMPACT Data Sharing Paradigm
Additional Features Revealed Through TIN Sequencin
Clinical Germline Assessment
Inferring Cancer Risk Through T/N Sequencing Tumor DNA
Prevalence of Clonal Hematopoiesis
Clonal Hematopoiesis Clinic at MSKCC
How Do Germline Variants Influence Somatic Phenoty
Prevalence of Pathogenic Mutations by Cancer Type
Prevalence of Biallelic Inactivation by Cancer Type
Many cancer are independent of the germline allele
Germline Contributions to Clonal Hematopoiesis?
Limitations of Tissue-Based DNA Sequencing
Genomic Profiling Using Plasma Cell-free DNA CFDNA
Rare Variant Detection: Ultra-Deep Sequencing & Erra Suppression
MSK-ACCESS for Plasma cfDNA Profiling
Clinical Implementation of MSK-ACCESS at MSK - Approved by NYS Department of Health in May 2019
Importance of Sequencing Matched Normal WBCs Identify and eliminate garming and clonal hematopoinsis variants
Polyclonal Acquired Resistance is commonly Observ
Additional Examples of Polyclonal Resistance Mutatic
Ongoing work: Increase sensitivity for detecting ctDN
Patients with Lynch Syndrome Develop MSI-H Tumors
Detecting MSi in cDNA Using MSK-ACCESS
Future Prospects for Clinical Sequencing • Incorporate more genes, non-coding regions, viral DNA
Acknowledgements: Molecular Diagnostics Service
Acknowledgements (Part 2)