Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
2017/08/14 by Maria Schwaederle, Maria Schwaederlé, Ranajoy Chattopadhyay +11 · 25 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer Genomics and Diagnostics #Lung Cancer Treatments and Mutations #Genetic factors in colorectal cancer
paper · doi:10.1158/0008-5472.can-17-0885
Abstract
Abstract Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419–27. ©2017 AACR.
Cited by
- Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system? [europepmc]
- Future of Liquid Biopsies With Growing Technological and Bioinformatics Studies: Opportunities and Challenges in Discovering Tumor Heterogeneity With Single-Cell Level Analysis. [europepmc]
- Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival. [europepmc]
- Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer. [europepmc]
- GNAS, GNAQ, and GNA11 alterations in patients with diverse cancers. [europepmc]
- Liquid Biopsy to Identify Actionable Genomic Alterations. [europepmc]
- Next-generation sequencing of prostate cancer: genomic and pathway alterations, potential actionability patterns, and relative rate of use of clinical-grade testing. [europepmc]
- Analysis of Circulating Tumor DNA and Clinical Correlates in Patients with Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma. [europepmc]
- Analysis of NTRK Alterations in Pan-Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics. [europepmc]
- The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis. [europepmc]
- Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival. [europepmc]
- Revisiting Epidermal Growth Factor Receptor ( EGFR ) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies. [europepmc]
- Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA. [europepmc]
- Performance of four platforms for KRAS mutation detection in plasma cell-free DNA: ddPCR, Idylla, COBAS z480 and BEAMing. [europepmc]
- The effect of surgical trauma on circulating free DNA levels in cancer patients-implications for studies of circulating tumor DNA. [europepmc]
- The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients. [europepmc]
- Targeting ERBB2 ( HER2 ) Amplification Identified by Next-Generation Sequencing in Patients With Advanced or Metastatic Solid Tumors Beyond Conventional Indications. [europepmc]
- Circulating tumour DNA in metastatic breast cancer to guide clinical trial enrolment and precision oncology: A cohort study. [europepmc]
- The Prognostic and Therapeutic Value of the Mutational Profile of Blood and Tumor Tissue in Head and Neck Squamous Cell Carcinoma. [europepmc]
- Molecular Profiling-Based Precision Medicine in Cancer: A Review of Current Evidence and Challenges. [europepmc]
- High prevalence of clonal hematopoiesis-type genomic abnormalities in cell-free DNA in invasive gliomas after treatment. [europepmc]
- Liquid Biopsies in Head and Neck Cancer: Current State and Future Challenges. [europepmc]
- Resection Margins in Head and Neck Cancer Surgery: An Update of Residual Disease and Field Cancerization. [europepmc]
- Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients. [europepmc]
- Liquid Biopsy and Primary Brain Tumors. [europepmc]
Related