APR 06, 2016 1:30 PM PDT

Validation and Implementation of Whole-Exome Sequencing to Guide Precision Cancer Care

Speaker

Abstract


Cancer remains the second leading cause of death in the United States.  Most tumors arise from a myriad of genetic changes that dysregulate cell growth and prompt survival.  Identification of genetic alterations by next generation sequencing (NGS), using either targeted sequencing or whole exome sequencing (WES) has become the standard of care in genomic medicine.  WES applies NGS technology to identify genetic variants in the coding regions (exons) of genes, harboring the majority of disease causing-mutations.  Using WES, it is currently feasible to not only detect a rapidly growing set of known clinically relevant mutations, but also identify novel or unexpected important variations, including constitutional mutations in cancer predisposing genes.  Thus far, the use of WES in cancer has largely taken place in the setting of large research studies.  Integration of WES into precision cancer care has lagged behind primarily due to technical challenges such as small and poor quality (FFPE) tissues and low-tumor purity samples that have not been rigorously validated in the clinical setting.  Another challenge is the analytical and computational approaches used to detect the wide-spectrum of mutations and genes queried by WES, which requires a comprehensive validation procedure to demonstrate the ability of the test to identify actionable mutations with high accuracy and at an acceptable analytical sensitivity.  The third challenge is a clinical challenge to attain meaningful interpretations of the genomic data which then can be used for patient care.  While these challenges are well recognized and despite a wide range of assays and platforms available, WES application in cancer has not yet been validated for the clinical laboratory and has not been fully characterized in the literature with regard to the analytic and clinical validity of the testing and the various types of relevant mutations.  The few existing guidelines given by professional societies give only high-level directions for implementing NGS testing geared primarily towards the use of targeted panels rather than WES.  By all accounts, New York State-Department of Health (NYS-DOH) requirements are among the most rigorous guidelines yet published and are likely to serve as a paradigm for suggested future type of guidelines that might be required by the Food and Drug Administration (FDA).  These efforts are also in line with the new precision medicine initiative announced by U.S. President Obama with the intent to bring us closer to curing cancer and give all of us access to a more personalized and genomic-driven medicine.
   This presentation describes the development and analytical characteristics of NYS-DOH approved clinical exome cancer test suitable for simultaneous detection of somatic dingle nucleotide variants (SNVs), indels and copy number alterations (CNAs) using the Agilent HaloPlex capture platform and the Illumina HiSeq2500 system for sequencing.  Initial validation has focused on actionable mutations in five principal, clinically relevant genes and according to NYS-DOH guidelines.  The automated computational framework for data analysis, variant interpretation and reporting is also discussed. 

The objectives of this presentation are:

  • To describe the development and analytical characteristics of a New York State-Department of Health (NYS-DOH) approved clinical Exome Cancer Test suitable for simultaneous detection of somatic single nucleotide variations (SNVs), indels and copy number alterations (CNAs). 
  • To discuss the automated computational framework for data analysis, variant interpretation and reporting of whole exome sequencing (WES) data, using examples of clinical cases and reporting of WES results. 

Show Resources
You May Also Like
FEB 15, 2023 7:00 AM PST
FEB 15, 2023 7:00 AM PST
Date: February 15, 2023 Time: 7:00am (PST), 10:00pm (EST), 4:00pm (CET) While not all microscopy samples can fluoresce, all can scatter light, and this scattered light can be imaged. This ha...
OCT 11, 2022 8:00 AM PDT
C.E. CREDITS
OCT 11, 2022 8:00 AM PDT
Date: October 11, 2022 Time: 8:00am (PDT), 11:00pm (EDT), 5:00pm (CEST) Multiomic profiling of cell populations at single-cell resolution is revolutionizing scientists’ understanding o...
AUG 16, 2022 11:00 AM PDT
AUG 16, 2022 11:00 AM PDT
Date: August 16, 2022 Time: 11:00am (PDT), 2:00pm (EDT), 8:00pm (CEST) Understanding genomic variation in the context of cancer is paramount to identifying disease drivers and informing pers...
C.E. CREDITS
Date: October 25, 2022 Time: 9:00am (PST), 12:00pm (EST), 6:00pm (CEST) Candida auris is a multi-drug resistant yeast that continues to be a global threat for infection and transmission in h...
AUG 24, 2022 7:00 AM PDT
AUG 24, 2022 7:00 AM PDT
Date: August 24, 2022 Time: 7:00am (PDT), 10:00pm (EDT), 4:00pm (CEST) Light field microscopy was first introduced in 2006, and allows users to capture the 4D light field within the microsco...
OCT 13, 2022 9:00 AM +08
OCT 13, 2022 9:00 AM +08
First Broadcast: Date: October 12, 2022 Time: 8:00am PDT, 11:00am EDT Second Broadcast: Date: October 12, 2022 Time: 9:00am SGT The new Embedded CryoSPARC Live, now fully integrated with t...
APR 06, 2016 1:30 PM PDT

Validation and Implementation of Whole-Exome Sequencing to Guide Precision Cancer Care



Show Resources
Loading Comments...
Show Resources