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This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous p53 , APC , KRAS , CDKN2A , and EGFR mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. BRAF , FBXW7 , PTEN , and SMAD4 mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: ATM , BRAF , CDKN2A , EGFR , FLT3 , GNA11 , KDR , KIT , PIK3CA , PTEN , PTPN11 , SMAD4 , and TP53 . In addition, APC , BRAF , FBXW7 , KRAS , SMAD4 , and TP53 mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of BRAF , SMAD4 , and TP53 genetic variants in the outcomes of patients with nCRT.

international journal of molecular sciences

Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy