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.
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.
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.
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
AstraZeneca, Sysmex, Merck
All authors have declared no conflicts of interest.