Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients

Abstract

Background: The incidence of colorectal cancer (CRC) in young adults has increased worldwide. Our study aimed to evaluate genomic alterations in early-onset (aged 15–39 years) sporadic CRC. Methods: Formalin-fixed, paraffin-embedded tissue samples from 90 patients with histologically confirmed colorectal adenocarcinoma with proficient mismatch repair status from Siriraj Hospital (Bangkok, Thailand) were extracted. Patients with clinically suspected familial adenomatous polyposis were excluded. A 517-gene mutational analysis was performed by next-generation sequencing using the Oncomine Comprehensive Assay Plus kit. The previously reported molecular data in adult-onset CRC from our group were used as a comparator group. Results: The five most frequently mutated genes were APC (66%), TP53 (51%), KRAS (47%), ARID1A (31%), and KMT2B (31%). When compare with adult-onset, NOTCH1 (11.1% vs. 1.9%), FBXW7 (23.3% vs. 14.8%), PIK3CA (20% vs. 12.1%), and FGFR3 (8.9% vs. 3.7%) mutations were more prevalent in early-onset. No differences were observed in other common mutations, such as TP53, EGFR, KRAS, NRAS and BRAF mutations. An increased prevalence in KRAS codon 12 mutations was also observed in early-onset patients compared to the adult-onset group (38.9% vs. 29.6%). Conclusions: Overall, the genomic landscape between early- and adult-onset CRC appears similar. However, our study revealed the enrichment of NOTCH1, FBXW7, PIK3CA, and FGFR3 along with KRAS G12 mutations, were more frequent in early-onset compared to adult-onset cases. Further studies with a larger cohort of patients on the comprehensive analysis of genetic/epigenetic signatures are required.