Journal Article

Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients

Ponvilawan, Ben, Sakornsakolpat, Phuwanat, Pongpaibul, Ananya, Korphaisarn, Krittiya, Roothumnong, Ekkapong, Pithukpakorn, Manop, Akewanlop, Charuwan

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adenocarcinoma - epidemiology / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Adenomatous polyposis coli / Adolescent / Adolescent and young adult / Adult / Age / Age factors in disease / Age of Onset / Analysis / Anopheles / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cdc4 protein / Codon / Colorectal cancer / Colorectal Neoplasms - epidemiology / Colorectal Neoplasms - genetics / Colorectal Neoplasms - pathology / Development and progression / DNA Mutational Analysis / Early onset / Epigenetics / Familial adenomatous polyposis / Female / Fibroblast growth factor receptors / Gene mutations / Genes / Genetic analysis / Genetic aspects / Genetic testing / Genomic alterations / Genomic analysis / Genomics - methods / Health aspects / Health Promotion and Disease Prevention / High-Throughput Nucleotide Sequencing / Humans / K-Ras protein / Male / Medical research / Medicine, Experimental / Medicine/Public Health / Mismatch repair / Molecular characteristic / Mutation / Next-generation sequencing / Oncology / p53 Protein / Patients / Polyps / Proto-Oncogene Proteins p21(ras) - genetics / Receptor, Notch1 / Surgical Oncology / Thailand - epidemiology / Tumor proteins / Young Adult / Young adults