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Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

Clinical utility of whole-genome sequencing in precision oncology

Richard Rosenquist¹, Edwin Cuppen², Reinhard Buettner³

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.

Seminars in Cancer Biology

|June 27, 2021

Abstract:

Precision diagnostics is one of the two pillars of precision medicine. Sequencing efforts in the past decade have firmly established cancer as a primarily genetically driven disease. This concept is supported by therapeutic successes aimed at particular pathways that are perturbed by specific driver mutations in protein-coding domains and reflected in three recent FDA tissue agnostic cancer drug approvals. In addition, there is increasing evidence from studies that interrogate the entire genome by whole-genome sequencing that acquired global and complex genomic aberrations including those in non-coding regions of the genome might also reflect clinical outcome. After addressing technical, logistical, financial and ethical challenges, national initiatives now aim to introduce clinical whole-genome sequencing into real-world diagnostics as a rational and potentially cost-effective tool for response prediction in cancer and to identify patients who would benefit most from 'expensive' targeted therapies and recruitment into clinical trials. However, so far, this has not been accompanied by a systematic and prospective evaluation of the clinical utility of whole-genome sequencing within clinical trials of uniformly treated patients of defined clinical outcome. This approach would also greatly facilitate novel predictive biomarker discovery and validation, ultimately reducing size and duration of clinical trials and cost of drug development. This manuscript is the third in a series of three to review and critically appraise the potential and challenges of clinical whole-genome sequencing in solid tumors and hematological malignancies.

Insights

Whole-genome sequencing (WGS) is crucial for precision cancer diagnostics. Systematic evaluation in clinical trials is needed to validate its utility for predicting treatment response and discovering biomarkers.

Area of Science:

Genomics
Oncology
Precision Medicine

Background:

Cancer is a genetically driven disease, with targeted therapies showing success.
Whole-genome sequencing (WGS) reveals complex genomic aberrations, including in non-coding regions, impacting clinical outcomes.
National initiatives aim to integrate WGS into clinical diagnostics for cancer treatment and clinical trial recruitment.

Purpose of the Study:

To critically appraise the potential and challenges of clinical whole-genome sequencing in solid tumors and hematological malignancies.
To highlight the need for systematic, prospective evaluation of WGS clinical utility in uniformly treated patient cohorts.
To discuss how WGS can facilitate biomarker discovery, reduce clinical trial costs, and improve drug development.

Main Methods:

Review and critical appraisal of existing literature on clinical whole-genome sequencing in cancer.
Analysis of the role of WGS in identifying genetic drivers and complex genomic aberrations.
Discussion of technical, logistical, financial, and ethical challenges associated with WGS implementation.

Main Results:

WGS supports the genetic basis of cancer and has potential for response prediction.
Evidence suggests genomic aberrations in non-coding regions correlate with clinical outcomes.
Current integration of WGS into diagnostics lacks systematic clinical utility evaluation in trials.

Conclusions:

Clinical whole-genome sequencing holds significant promise for precision cancer diagnostics and personalized therapy.
Prospective clinical trials are essential to validate WGS utility, discover biomarkers, and optimize cancer care.
Addressing challenges is key to realizing the full potential of WGS in oncology.

Read full analysis

Keywords:

Clinical utility Genomics Precision cancer medicine Risk stratification Whole-genome sequencing

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