Related Experiment Video
Updated: Mar 27, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comprehensive Genomic and Transcriptomic Analysis to Guide Therapy for Patients with Metastatic Solid Tumors
Burak Uzunparmak1, Fei Su2, Amber Johnson2
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract:
The added value of comprehensive genomic and transcriptomic profiling (CGTP) with whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) as compared with conventional targeted panel-based sequencing is not well-characterized for patients with cancer. We thus sought to determine the potential clinical utility of CGTP in a prospective clinical study in patients with advanced or metastatic solid tumors. We performed WES and WTS for patients who had prior targeted panel sequencing and had no DNA alterations with approved biomarker-matched therapies. We analyzed CGTP data of 99 patients with advanced cancers across 19 solid tumor types and assessed the presence of actionable DNA alterations and RNA expressions linked to approved or investigational agents. CGTP identified actionable genomic and transcriptomic alterations in 69.7% and 100% of cases, respectively. In this pilot study in which CGTP was incorporated into routine care, 19.2% of patients received biomarker-matched therapy.
Significance:
This study demonstrates the feasibility and utility of extensive genomic and transcriptomic profiling to match patients with advanced cancer to molecularly informed treatments. Transcriptomic actionability analysis identifies actionable RNA expressions for patients beyond those with actionable DNA alterations, highlighting the potential of transcriptional profiling to enhance therapeutic opportunities in precision oncology.
Insights
Comprehensive genomic and transcriptomic profiling (CGTP) using whole exome sequencing (WES) and whole transcriptome sequencing (WTS) shows significant clinical utility in advanced cancer patients. CGTP identified actionable alterations in most cases, enabling targeted therapy selection.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- The clinical utility of comprehensive genomic and transcriptomic profiling (CGTP) compared to targeted panels is not well-defined for cancer patients.
- Advanced or metastatic solid tumors often lack actionable targets identified by conventional sequencing methods.
Purpose of the Study:
- To prospectively evaluate the clinical utility of CGTP, integrating whole exome sequencing (WES) and whole transcriptome sequencing (WTS).
- To assess the identification of actionable genomic and transcriptomic alterations in patients with advanced cancers who had prior negative targeted panel sequencing.
Main Methods:
- Prospective clinical study involving 99 patients with advanced solid tumors across 19 types.
- Performed WES and WTS on patients with prior targeted panel sequencing and no identified biomarker-matched therapies.
- Analyzed CGTP data for actionable DNA alterations and RNA expressions linked to approved or investigational agents.
Main Results:
- CGTP identified actionable genomic alterations in 69.7% of patients.
- Actionable transcriptomic alterations were identified in 100% of patients.
- 19.2% of patients received biomarker-matched therapy in this pilot study integrating CGTP into routine care.
Conclusions:
- CGTP demonstrates significant potential clinical utility in advanced cancer patients, revealing actionable targets missed by targeted panels.
- Integrating WES and WTS provides a comprehensive molecular profile, increasing opportunities for biomarker-matched therapies.
- Further studies are warranted to confirm the impact of CGTP on patient outcomes in routine clinical practice.
