Performance Comparison of Two Next-Generation Sequencing Panels to Detect Actionable Mutations in Cell-Free DNA in Cancer Patients. Scientific Publication

Jul 28, 2020 | Magazine: Clinical Chemistry and Laboratory Medicine

Mónica Macías (1) , Eva Cañada-Higueras (2) , Estibaliz Alegre (1, 3) , Arancha Bielsa (2) , Javier Gracia (2) , Ana Patiño-García (2, 3, 4) , Roser Ferrer-Costa (5) , Teresa Sendino (1) , María P Andueza (6) , Beatriz Mateos (1) , Javier Rodríguez (3, 6) , Jesús Corral (2) , Alfonso Gúrpide (3, 6) , José M Lopez-Picazo (3, 6) , Jose L Perez-Gracia (3, 6) , Ignacio Gil-Bazo (3, 6, 7, 8) , Gorka Alkorta-Aranburu (2) , Álvaro González (1, 3)

Background

Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Next-generation sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms.

Here we compare two NGS panels for cfDNA: Oncomine™ Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360® (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory.

Methods

Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360® (G360) was requested as part of their clinical assistance.

Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with Oncomine™ Pan-Cancer (OM) panel in an Ion GeneStudio S5™ System.

Results

cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01).

Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM.

Conclusions

In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.

CITATION Clin Chem Lab Med . 2020 Jul 28;58(8):1341-1348. doi: 10.1515/cclm-2019-1267

see publication in pubmed