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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 tumor sequencing: opportunities and challenges for precision cancer medicine
Senthilkumar Damodaran1, Michael F Berger1, Sameek Roychowdhury1
1From the Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH; Memorial Sloan Kettering Cancer Center, New York, NY; Department of Pharmacology, The Ohio State University, Columbus, OH.
Abstract:
Advances in tumor genome sequencing have enabled discovery of actionable alterations leading to novel therapies. Currently, there are approved targeted therapies across various tumors that can be matched to genomic alterations, such as point mutations, gene amplification, and translocations. Tools to detect these genomic alterations have emerged as a result of decreasing costs and improved throughput enabled by next-generation sequencing (NGS) technologies. NGS has been successfully utilized for developing biomarkers to assess susceptibility, diagnosis, prognosis, and treatment of cancers. However, clinical application presents some potential challenges in terms of tumor specimen acquisition, analysis, privacy, interpretation, and drug development in rare cancer subsets. Although whole-genome sequencing offers the most complete strategy for tumor analysis, its present utility in clinical care is limited. Consequently, targeted gene capture panels are more commonly employed by academic institutions and commercial vendors for clinical grade cancer genomic testing to assess molecular eligibility for matching therapies, whereas whole-exome and transcriptome (RNASeq) sequencing are being utilized for discovery research. This review discusses the strategies, clinical challenges, and opportunities associated with the application of cancer genomic testing for precision cancer medicine.
Insights
Next-generation sequencing (NGS) enables precision cancer medicine by identifying actionable genomic alterations for targeted therapies. Challenges in clinical application include specimen handling, interpretation, and drug development for rare cancers.
Area of Science:
- Genomic Medicine
- Oncology
- Biotechnology
Background:
- Tumor genome sequencing advances have identified actionable alterations, leading to novel targeted therapies for various cancers.
- Next-generation sequencing (NGS) technologies have decreased costs and improved throughput for detecting genomic alterations.
- NGS is crucial for developing biomarkers for cancer susceptibility, diagnosis, prognosis, and treatment.
Purpose of the Study:
- To review strategies for applying cancer genomic testing in precision cancer medicine.
- To discuss the clinical challenges and opportunities associated with cancer genomic testing.
- To highlight the role of different sequencing approaches in clinical care and research.
Main Methods:
- Review of current literature and clinical practices in cancer genomic testing.
- Discussion of targeted gene capture panels for clinical-grade testing.
- Exploration of whole-exome and transcriptome sequencing (RNASeq) for discovery research.
Main Results:
- Targeted gene panels are commonly used for clinical assessment of molecular eligibility for therapies.
- Whole-genome sequencing offers comprehensive analysis but has limited current clinical utility.
- NGS enables biomarker development for various aspects of cancer management.
Conclusions:
- Cancer genomic testing is pivotal for advancing precision cancer medicine.
- Clinical implementation faces challenges in specimen acquisition, analysis, privacy, interpretation, and rare cancer drug development.
- A combination of targeted panels for clinical use and broader sequencing for research is currently employed.
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