Changes in KRAS mutations in patients with oral mucosa and tongue cancer (OMTC) undergoing medical treatment with cetuximab (Cet).

Abstract

e17524 Background: Mutations in KRAS are known to be predictors of anti-EGFR therapy efficacy. Besides the mutation status of the treatment-naive tumors the changes in the level of mutant DNA during medical treatment are also of clinical interest for the individualization of the treatment. The purpose of the study was to detect somatic single nucleotide polymorphism (SNP) activating mutations in KRAS exon 2 in patients (pts) with OMTC undergoing chemotherapy (CT)±Cetuximab (Cet). Methods: Extracellular DNA samples were obtained from plasma of pts with OMTC (T3-4No-1Mo) undergoing CT (CDDP+5FU)+Cet (group A) before treatment and in 2 weeks after. Patients undergoing CT (CDDP+5FU, no Cet) were included in Group B. 7 activating mutations in KRAS exon 2 were detected by Droplet Digital PCR method (DD PCR) with "KRAS Screening Multiplex Kit" (BioRad, USA). Results: Samples from 28 pts were included. The frequency of SNP activating in KRAS exon 2 before treatment was 25%. In the group A (n = 12) KRAS mutations were not found or the level of mutant DNA did not exceed 1%. No significant changes were found in this group after treatment. The group B (n = 16) had some KRAS variations the majority of which did not change after treatment. However, 2 pts had a sharp increase in mutant DNA: from 0.03% before CT in both cases to 17.04% and 56.38% -after treatment (p < 0.01). Conclusions: Medical treatment, especially CT, could cause the changes in activating mutations in KRAS exon 2 in pts with OMTC. Revealing of these changes is of great importance for the following treatment options. Detection of mutant extracellular DNA by DD PCR could be valuable to monitor their status during the treatment.