Related Experiment Video
Updated: Jun 18, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Unique genomic alterations in the circulating tumor DNA of patients with solid tumors brain metastases
Laura Alder1, Gloria Broadwater2, Michelle Green3
1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina, USA.
Background:
Although serum circulating tumor DNA (ctDNA) is routine, data from patients with brain metastases (BrMs) is limited. We assessed genomic alterations in ctDNA from patients with solid tumor BrMs in 3 groups: Isolated BrMs with stable extracranial disease (iCNS), concurrent brain and extracranial progression (cCNS), and extracranial progression with no active BrMs (eCNS). We also compared ctDNA alterations between patients with and without BrMs.
Methods:
Patients with a Guardant360 ctDNA profile with (n = 253) and without BrMs (n = 449) from the Duke Molecular Registry between January 2014 and December 2020 were identified. Actionable alterations were defined as FDA-recognized or standard-of-care biomarkers. Disease status was determined via investigator assessment within 30 days of ctDNA collection.
Results:
Among the 253 patients with BrMs: 29 (12%) had iCNS, 160 (63%) cCNS, and 64 (25%) eCNS. Breast (BC; 12.0%) and non-small cell lung cancer (NSCLC; 76.4%) were the most common tumor types. ESR1 (60% vs 25%, P < .001) and BRCA2 (17% vs 5%, P = .022) were more frequent in BC BrMs. In NSCLC BrMs, EGFR alterations were most frequent in the iCNS group (iCNS: 67%, cCNS: 40%, eCNS:37%, P = .08) and in patients with BrMs (36% vs 17%, P < .001). Sequencing from both brain tissue and ctDNA were available for 8 patients; 7 (87.5%) had identical alterations.
Conclusions:
This study illustrates the feasibility of detecting alterations from ctDNA among patients with BrMs. A higher frequency of actionable mutations was observed in ctDNA in patients with BrMs. Additional studies comparing ctDNA and alterations in BrMs tissue are needed to determine if ctDNA can be considered a surrogate to support treatment decisions.
Related Concept Videos
Cancers Originate from Somatic Mutations in a Single Cell
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Treatment Resistant Cancers
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Cancers Originate from Somatic Mutations in a Single Cell

