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

Abstract

PURPOSE The combination of whole-genome and transcriptome sequencing (WGTS) is expected to transform diagnosis and treatment for patients with cancer. WGTS is a comprehensive precision diagnostic test that is starting to replace the standard of care for oncology molecular testing in health care systems around the world; however, the implementation and widescale adoption of this best-in-class testing is lacking. METHODS Here, we address the barriers in integrating WGTS for cancer diagnostics and treatment selection and answer questions regarding utility in different cancer types, cost-effectiveness and affordability, and other practical considerations for WGTS implementation. RESULTS We review the current studies implementing WGTS in health care systems and provide a synopsis of the clinical evidence and insights into practical considerations for WGTS implementation. We reflect on regulatory, costs, reimbursement, and incidental findings aspects of this test. CONCLUSION WGTS is an appropriate comprehensive clinical test for many tumor types and can replace multiple, cascade testing approaches currently performed. Decreasing sequencing cost, increasing number of clinically relevant aberrations and discovery of more complex biomarkers of treatment response, should pave the way for health care systems and laboratories in implementing WGTS into clinical practice, to transform diagnosis and treatment for patients with cancer.

Simultaneous Ultra-Sensitive Detection of Structural and Single Nucleotide Variants Using Multiplex Droplet Digital PCR in Liquid Biopsies from Children with Medulloblastoma

“…In addition, WGS data will be the key to the implementation of new and more precise therapeutic strategies that are currently being developed. WGS is not globally available, but in some countries, WGS profiling of tumors is becoming standard procedure for diagnostics, at least for certain cancer types such as pediatric cancer (e.g., via Genomic Medicine Sweden), and in these countries, it is reasonable to make use of the data for MRD assessment [ 20 , 63 ]. Rapidly decreasing sequencing costs will likely also stimulate the gradual implementation of WGS in cancer diagnostics in the near future.…”

“…Recent studies using whole-genome sequencing (WGS) and other high-throughput technologies have transformed cancer research by greatly expanding our knowledge of the genetic events that drive malignant transformation in pediatric cancers in general [ 14 , 15 , 16 ] and in MBs specifically [ 17 , 18 ]. These techniques are increasingly being implemented in the clinical setting and have the advantage of providing a comprehensive map of the clonal genetic aberrations that can potentially be used as biomarkers [ 19 , 20 ].…”

A complete digital karyotype of the B-cell leukemia REH cell line resolved by long-read sequencing

“…Traditional karyotyping and banding techniques can resolve structural variants to a resolution of 5Mbp, while FISH and microarray analyses are limited to approximately 150kbp 11,12 . Whole genome and transcriptome sequencing (WGTS) have become increasingly important as a comprehensive clinical test for accurately resolving genomic breakpoints of structural variants (SVs) and fusion genes in cancer genomes, providing significant improvements in diagnostic yield over analog methods [13][14][15] . Sequencing-based diagnostic approaches are predominantly based on short-read next generation sequencing (NGS) technologies, which have benefits in low cost, high accuracy, and extensively validated computational pipelines [16][17][18] .…”

The FIRST-Dx Study Takes Steps Toward Personalized Cancer Therapy

“…The rate of patients receiving molecular tumor board-derived targeted therapy might seem low; however, it is much better than early studies in which few patients with tumor molecular profiling could be allocated to a therapy based on specific genetic alterations . One of the obstacles for putting molecular profiling to the forefront of clinical decision-making remains the analysis of complex data, especially since we are moving toward whole genome and exome sequencing plus transcriptome rather than panels . Here, a holistic approach is required, looking at the entirety of the genetic information.…”

“…3 One of the obstacles for putting molecular profiling to the forefront of clinical decision-making remains the analysis of complex data, especially since we are moving toward whole genome and exome sequencing plus transcriptome rather than panels. 4 Here, a holistic approach is required, looking at the entirety of the genetic information. This requires artificial intelligence-supported software to deploy the fullness of biomarkers in evidence-based treatment recommendations.…”