Research Papers:

Application of cell-free DNA for genomic tumor profiling: a feasibility study

Lise B. Ahlborn _, Kristoffer S. Rohrberg, Migle Gabrielaite, Ida V. Tuxen, Christina W. Yde, Iben Spanggaard, Eric Santoni-Rugiu, Finn C. Nielsen, Ulrik Lassen, Morten Mau-Sorensen and Olga Østrup

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Oncotarget. 2019; 10:1388-1398. https://doi.org/10.18632/oncotarget.26642

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Lise B. Ahlborn1,2, Kristoffer S. Rohrberg1, Migle Gabrielaite2, Ida V. Tuxen1, Christina W. Yde2, Iben Spanggaard1, Eric Santoni-Rugiu3, Finn C. Nielsen2, Ulrik Lassen1, Morten Mau-Sorensen1,*, Olga Østrup2,*

1The Phase I Unit, Department of Oncology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

2Center for Genomic Medicine, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

3Department of Pathology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

*These authors contributed equally to this work

Correspondence to:

Lise B. Ahlborn, email: [email protected]

Keywords: cfDNA; liquid biopsy; genomic profile; biopsy; WES

Received: October 24, 2014     Accepted: January 17, 2019     Published: February 15, 2019


Purpose: Access to genomic tumor material is required to select patients for targeted therapies. However, tissue biopsies are not always feasible and therefore circulating cell-free DNA (cfDNA) has emerged as an alternative. Here we investigate the utility of cfDNA for genomic tumor profiling in the phase I setting.

Study design: Peripheral blood was collected from patients with advanced solid cancers eligible for phase I treatment. Patients failing the initial tissue biopsy due to inaccessible lesions or insufficient tumor cellularity (<10%) were included in the study. Genomic profiling of cfDNA including whole exome sequencing (WES) and somatic copy number alterations (SCNAs) analysis (OncoScan).

Results: Plasma cfDNA was pro- and retrospectively profiled from 24 and 20 patients, respectively. The median turnaround time was 29 days (N= 24, range 13-87 days) compared to tissue re-analyses of median 60 days (N= 6, range 29-98). Selected cancer-associated alterations (SCAAs) were identified in 70% (31/44) of patients, predominantly by WES due to the low sensitivity of OncoScan on cfDNA. Primarily, inaccessible cases of prostate and lung cancers could benefit from cfDNA profiling. In contrast, breast cancer patients showed a low level of tumor-specific cfDNA which might be due to cancer type and/or active treatment at the time of plasma collection.

Conclusion: Plasma cfDNA profiling using WES is feasible within a clinically relevant timeframe and represents an alternative to invasive tissue biopsies to identify possible treatment targets. Especially, difficult-to-biopsy cancers can benefit from cfDNA profiling, but tumor tissue remains the gold standard for molecular analyses.

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