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The Implementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care

New York, NY  ·  January 25, 2023
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The New York Genome Center (NYGC) is proud to have collaborated on this multi-institutional article which addresses the requirements for integrating whole-genome transcriptome sequencing into health care systems.

How can whole-genome transcriptome sequencing (WGTS) be integrated into health care systems to replace the standard of care for oncology? The next-generation comprehensive precision diagnostic test has the potential to become the best practice for oncology molecular testing in health care systems around the world, and yet the implementation and wide-scale adoption of the best-in-class testing is lacking.

WGTS for oncology is a complex genetic test that involves sequencing the genome of the tumor, the matched normal (unaffected) specimen, and the transcriptome of the tumor specimen. Unlike gene panels or whole exome sequencing, WGTS is a comprehensive test replacing several individual molecular tests. This allows WGTS to make more efficient use of scarce tumor material, especially in the case of smaller biopsies.

Dr. Vaidehi Jobanputra, PhD, FACMG, Chief Diagnostics Officer at NYGC and a participant in the panel.

Two years ago, a panel made up of 25 global experts in the fields of oncology, pathology, genetics, translational research, and health technology assessment, began a series of informal meetings to discuss the barriers that may arise when health care systems begin to integrate WGTS for cancer diagnostics and treatment selection. Their findings, recently published in JCO Precision Oncology, address the utility of WGTS in different cancer types, cost-effectiveness, affordability, and other practical considerations for the implementation such as technology, health economics and reimbursement, clinical evidence needs, and data analysis and interpretation.

This panel included the New York Genome Center (NYGC) Chief Diagnostics Officer, Vaidehi Jobanputra, PhD, FACMG. Dr. Jobanputra also leads the Clinical Lab at NYGC, where the first whole-genome and transcriptome sequencing oncology test was developed and approved for clinical testing by the New York State Department of Health.

“This publication is just the beginning of a broader conversation international experts must have to shed light on the necessary actions performed by health care systems to prepare for the WGTS transformation, and to bring these new developments to patients with cancer,” explains Dr. Jobanputra, the paper’s senior author.

How can health care systems prepare to implement WGTS into clinical practice?
The panel compiled several aspects that must be considered by health care systems when integrating WGTS into their routine oncology diagnostic testing, including the following:

  • Sample collection and biobanking
    Currently, formalin fixed, paraffin-embedded (FFPE) samples are routinely collected sample types in most clinical laboratories and fresh frozen (FF) samples are available in only a limited number of centers. FF samples are preferred as they are less noisy in genome-wide analysis of some variant types. However, routine collection of FF samples and standardized biobanking creates logistic and infrastructure issues.

The Hartwig Medical Foundation and 100.000 Genomes Project in the United Kingdom showed that WGS can be performed on FFPE and provides similar diagnostic accuracy of known driver mutations as panels. Additionally, The New York Genome Center has validated FFPE specimens for whole genome sequencing and whole transcriptome sequencing. Since FFPE tumor samples do still bring key value to initial diagnoses based on histopathologic evaluation and tumor type classification and staging, a likely future scenario is that FFPE specimen will be collected for histology as well as FF biopsies for molecular diagnostics.

  • Data analysis, interpretation, and reporting
    Small labs may face a challenge when analyzing, interpreting and reporting complex tests as WGTS. Institutes may consider specialized centers for WGTS diagnostics for comprehensive data analysis, including flexible and more automated solutions for clinical interpretation, reporting, and data storage, which will not only improve diagnostic efficiency and precision but also reduce costs and analysis infrastructure required to implement WGTS.


  • Regulatory approval
    Regulatory approval of WGTS tests is likely to pose challenges as validation of all variant types across cancer types is a daunting task. Importantly, as WGTS involves the possibility of incidental germline findings, specific attention is required for implementing appropriate counseling, consenting, and opt-out procedures, following regional regulations and laws. Overall, assay validation of WGTS follows the same basic principles for validating other molecular tests. As the field matures and the laboratories gain experience, it is expected that these guidelines will evolve.


  • Reimbursement landscape
    While coverage and reimbursement of germline WGS has accelerated in recent years for pediatric patients with suspected genetic diseases, there is currently little-to-no coverage for oncology WGS applications in the United States. When testing is performed for patients in the inpatient setting, hospitals are generally reimbursed through a bundled diagnosis-related group rate. Therefore, specific coverage of a test is not required, and tumor types where WGTS offsets the aggregated cost of performing traditional SoC tests are likely to be adopted faster. In the outpatient setting, insurance coverage will be dictated through coverage policies.


The future of WGTS
Going forward, WGTS can also be used as a learning system for oncology diagnostics where clinicians use cumulative WGTS data, clinical and outcome data, and machine learning and artificial intelligence (AI) approaches as a guide in “patients-like-mine” assessments. The assessment would identify pathogenic markers to guide treatment, allow patient-group stratifications to enable targeted rather than conventional treatment, expand access to treatment options, and accelerate the development of new drugs.

A refined diagnosis may prevent patients from being misassigned to therapies that are unlikely to provide any efficacy, which could increase the patient’s life expectancy.

“The implementation of WGTS has the potential to transform diagnosis and treatment for patients with cancer and identify new biomarkers for improved risk stratification and reduction of overtreatment. This is important because newly developed, targeted therapies can be life-saving game-changers in some patients,” adds Dr. Jobanputra.

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