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 · 108 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Bioinformatics #Biology #Cancer #Cancer Genomics and Diagnostics #Cancer research #Circulating tumor DNA #Cohort #Colorectal cancer #DNA #DNA sequencing #Genetic factors in colorectal cancer #Genetics #Internal medicine #KRAS #Lung Cancer Treatments and Mutations #Lung cancer #Medicine #Oncology #Pathology #Personalized medicine #Precision medicine
paper · open access · doi:10.1158/0008-5472.can-17-0885
published in Cancer Research 77(19), 5419-5427 (American Association for Cancer Research)
openalex publication_date 2017/08/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.
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