Detection of Three Distinct Clonal Populations Using Circulating Cell-Free DNA: A Cautionary Note on the Use of Liquid Biopsy

Riedlinger, Gregory; Jalloul, Nahed; Poplin, Elizabeth; Mehnert, Janice M.; Groisberg, Roman; Khiabanian, Hossein; Ganesan, Shridar

doi:10.1200/po.19.00193

Cited by 1 publication

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“…By contrast, the increasingly high sensitivity of sequencing technologies can introduce potentially confounding factors such as the detection of somatic mutations deriving from normal tissues, in particular clonal hematopoiesis of indeterminate potential. 23 , 24 This could also explain the higher incidence of co-occurring TP53 mutations, with respect to public databases. In our study, we did not concurrently sequence paired white blood cells to rule out clonal hematopoiesis of indeterminate potential.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Dynamics of Circulating Tumor Cells and Circulating Tumor DNA for Treatment Monitoring in Metastatic Breast Cancer

Gerratana

Davis

Zhang

et al. 2021

JCO Precision Oncology

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PURPOSE Liquid biopsy–based biomarkers, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). The aim of the study was to explore CTCs and ctDNA dynamics to better understand their potentially complementary role in describing MBC. METHODS The study retrospectively analyzed 107 patients with MBC characterized with paired CTCs and ctDNA assessments and a second prospective cohort, which enrolled 48 patients with MBC. CTCs were immunomagnetically isolated and ctDNA was quantified and then characterized through next-generation sequencing in the retrospective cohort and droplet digital polymerase chain reaction in the prospective cohort. Matched pairs variations at baseline, at evaluation one (EV1), and at progression were tested through the Wilcoxon test. The prognostic role of ctDNA parameters was also investigated. RESULTS Mutant allele frequency (MAF) had a significant decrease between baseline and EV1 and a significant increase between EV1 and progression. Number of detected alterations steadily increased across timepoints, CTCs enumeration (nCTCs) significantly increased only between EV1 and progression. MAF dynamics across the main altered genes was then investigated. Plasma DNA yield did not vary across timepoints both in the retrospective cohort and in the prospective cohort, while the short fragments fraction showed a potential role as a prognostic biomarker. CONCLUSION nCTCs and ctDNA provide complementary information about prognosis and treatment benefit. Although nCTCs appeared to assess tumor biology rather than tumor burden, MAF may be a promising biomarker for the dynamic assessment of treatment response and resistance.

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Section: Discussionmentioning

confidence: 99%