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Poster display session

3577 - Comparison of performances of three technologies for detection of RAS mutations in cfDNA (NGS strategy, BEAMing assay and ddPCR BioRAD assay)

Date

09 Sep 2017

Session

Poster display session

Topics

Translational Research;  Colon and Rectal Cancer

Presenters

Jessica Garcia

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

J. Garcia1, J. Forestier2, E. Dusserre1, C. Rodriguez-Lafrasse3, V. Cheynet4, A.S. Wosny1, C. Ferraro Peyret5, K. Brengel-Pesce6, M. Guillet2, M. Chauvenet7, S. Couraud8, M. Brevet9, T. Walter2, L. Payen10

Author affiliations

  • 1 Biochemistry And Molecular Biology, Hospices Civils of LYON, 69008 - LYON/FR
  • 2 Clinical Department, Hospices Civils of LYON, 69003 - LYON/FR
  • 3 Biochemistry And Molecular Biology, Hospices Civils of LYON, 69008 - Lyon/FR
  • 4 Biomerieux, Hospices Civils of LYON, 69003 - LYON/FR
  • 5 Pathology, Hospices Civils of LYON, 6900 - LYON/FR
  • 6 Biomerieux, Hospices Civils of LYON, 6900 - Lyon/FR
  • 7 Clinical Department, Hospices Civils of LYON, 69002 - LYON/FR
  • 8 Clinical Department, Centre Hospitalier Lyon Sud, 69495 - Pierre Bénite/FR
  • 9 Pathology, Hospices Civils of LYON, 69002 - LYON/FR
  • 10 Biochemistry And Molecular Biology, Hospices Civiles de Lyon, 69002 - Lyon/FR
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Resources

Abstract 3577

Background

A number of RAS mutations confer resistance to anti-EGFR treatments used in the management of colon cancer. The objective of this study was to evaluate the ability of cell-free plasma DNA (cfDNA) to reflect the mutational status of a tumor in order to use liquid biopsies instead of invasive and painful solid tumor biopsies when monitoring tumor progression.

Methods

We selected tumors from the CIRCAN_0 cohort. The molecular profiles from solid biopsies were routinely assessed with the PGM NGS technology. Plasma samples were collected at diagnosis (colon cancer) and during progression (lung cancer). KRAS and NRAS somatic alterations were quantified using three different technologies: droplet digital polymerase chain reaction (ddPCR) from BioRad and BEAMing (Oncobeam) from Sysmex Innostics, as well as next generation sequencing (NGS, NextSEQ500 by Illumina) using the library prepared with the 56G oncology panel kit from Swift Biosciences.

Results

The highly sensitive and specific assays enabled us to obtain excellent matches with solid biopsies determined in cfDNA for colon cancer at diagnosis and for lung cancer during disease progression. When examining cfDNA from patients displaying mutations in their colon biopsy for one of the KRAS and/or NRAS mutations, 100% of the mutations were confirmed using the OncoBEAM technology, whereas only 66% matched the initial PGM status using the two other technologies. The BEAMing technology enabled us to detect KRAS mutations in patients with negative biopsy, increasing the detection of the KRAS positive profiles compared to the standard solid biopsy method. cfDNA was sampled during progression and the high sensitivity and reproducibility of the BEAMing technology enabled us to identify patients with KRAS persistence and others, developing an additional mechanism of relapse.

Conclusions

The advantage of the NGS technology is the larger coverage of longer gene regions for screening purposes, while the BEAMing technology provides highly sensitive results allowing us to follow the kinetics of appearance and disappearance of somatic alterations, linked to the efficiency of therapies.

Clinical trial identification

Legal entity responsible for the study

Hospices Civils of Lyon

Funding

AstraZeneca, Sysmex, Merck

Disclosure

All authors have declared no conflicts of interest.

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