Abstract 406P
Background
Neoadjuvant chemoradiotherapy (nCRT) is a common treatment option for the locally advanced rectal cancer. Many studies demonstrate that residual tumor tissues, which are obtained after neoadjuvant treatment, differ in their characteristics as compared to the treatment-naïve neoplasms. We investigated whether nCRT resulted in the changes of the status of driver mutations in rectal carcinomas.
Methods
The study included 101 patients with rectal cancer, who failed to achieve complete pathologic response upon nCRT. KRAS, NRAS and BRAF mutations were analyzed in paired pre- and post-nCRT tumor samples by conventional techniques (allele-specific PCR, droplet digital PCR and Sanger sequencing).
Results
61 of 101 (60.4%) primary tumors contained mutations in KRAS, NRAS or BRAF genes. Two of these carcinomas had signals for two mutated alleles involving the same gene (KRAS G12V/G12D and NRAS G12S/Q61L); the remaining 59 tumors showed the presence of a single mutation. All analyzed tumors had the same spectrum of mutations before and after nCRT. However, tumors with double mutations demonstrated changes in the ratio between mutated alleles upon nCRT.
Conclusions
Neoadjuvant chemoradiotherapy does not change the status of driver mutations in rectal carcinomas. This study also suggests, that a small proportion of colorectal cancers indeed carries more than one somatic mutation in KRAS, NRAS and BRAF genes; this phenomenon is likely to the attributed to intratumoral clonal heterogeneity, but not to the simultaneous somatic activation of both paternal and maternal alleles of the same gene.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study has been supported by the Russian Science Foundation (grant 20-75-10163).
Disclosure
All authors have declared no conflicts of interest.