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. 2021 Jan;21(1):15.
doi: 10.3892/ol.2020.12276. Epub 2020 Nov 6.

KRAS and NRAS mutation detection in circulating DNA from patients with metastatic colorectal cancer using BEAMing assay: Concordance with standard biopsy and clinical evaluation

Elena Lastraioli  1 , Lorenzo Antonuzzo  2 , Beatrice Fantechi  2 , Luisa Di Cerbo  2 , Alessandro Di Costanzo  2 , Daniele Lavacchi  2 , Miriam Armenio  1 , Annarosa Arcangeli  1 , Francesca Castiglione  3 , Luca Messerini  1 , Francesco Di Costanzo  2
Affiliations

KRAS and NRAS mutation detection in circulating DNA from patients with metastatic colorectal cancer using BEAMing assay: Concordance with standard biopsy and clinical evaluation

Elena Lastraioli et al. Oncol Lett. 2021 Jan.

Abstract

Patients with metastatic colorectal cancer (mCRC) are routinely screened for either K- and N-RAS to select the appropriate treatment. The present study aimed to evaluate the concordance between K- and NRAS status in the tissue (either primary tumor or metastasis) and the plasma of patients with mCRC and to identify the associations between K- and NRAS mutations in ctDNA and the clinicopathological parameters. Samples from a total of 31 patients with mCRC with measurable disease according to the Response Evaluation Criteria in Solid Tumors were analyzed. For all patients, K- and NRAS status was determined in the tissue by matrix-assisted laser desorption/ionization time of flight mass spectrometry. For the detection of RAS mutations in cell-free tumor DNA also defined as circulating tumor DNA (ctDNA), the OncoBEAM® RAS CRC kit (Sysmex Inostics) was used. A total of 6/31 tissue samples expressed wild-type KRAS, whereas 25/31 presented mutations. In addition, 7/31 plasma samples expressed wild-type KRAS, mutations were detected in 22/31 patients, and for 2/31 patients, the test did not provide a conclusive result. A total of 24/31 patients expressed wild-type NRAS, 6/31 had mutations and 1/21 was not informative. For the KRAS mutational status, a moderate concordance (agreement, 85.18%; Cohen's k, 0.513) between the tissue and plasma analysis was observed; for NRAS, a fair agreement (agreement, 83.33%; Cohen's k, 0.242) was obtained. In conclusion, both tissue and plasma analyses should be performed for the management of patients with mCRC. To better exploit the beads, emulsions, amplification, magnetics (BEAMing) technique in the clinical setting, studies aimed at determining the RAS status to monitor therapy and during follow-up are warranted.

Keywords: KRAS; NRAS; beads; emulsions amplification; magnetics; mass spectrometry; metastatic colorectal cancer.

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Figures

Figure 1.
Figure 1.
Representative plots obtained by BEAMing assay. In the left plot of each panel ‘universal signal’ vs. ‘mutant signal’ is reported, whereas in the right plot, ‘wild-type signal’ vs. ‘mutant signal’ is presented. (A) Negative control; (B) PC; mutant beads, 844; mutant fraction, 0.46%; (C) WT; mutant beads, 14; mutant fraction, 0.02%; (D) MUT; mutant beads, 14,746; mutant fraction, 7.645 (see arrow). EB, extended beads; NEB, non-extended beads; wt, wild-type; mx, mutant and wild-type; mt, mutant; NTC, no template control; PC, positive control; WT, wild-type sample; MUT, mutant sample.
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