What does this research mean for the field?

Early-onset colorectal cancer exhibits a distinct genomic profile compared to late-onset disease, characterized by an increased prevalence of KRAS G12D, FBXW7, NF1, and POLE mutations, and a lower prevalence of BRAF V600E, KRAS G12V, and CDK12 truncations. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study investigates the clinical and genomic characteristics of early-onset colorectal cancer compared to late-onset colorectal cancer.

May 30, 2026

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Targetable genomic alterations in early-onset colorectal cancer and their therapeutic implications: Real-world data.

YMYostena MekhailThe Christie NHS Foundation Trust KKKonstantinos Vellios KamposiorasThe Christie Hospital

Key Points

This study investigates the clinical and genomic characteristics of early-onset colorectal cancer compared to late-onset colorectal cancer.
Patients with colorectal cancer were analyzed from two public datasets: GENIE Biopharma Collaborative and GENIE Cohort.
Patients were stratified into early-onset and late-onset groups based on age during genomic sequencing.
Genomic alterations were evaluated for therapeutic implications using OncoKB.
Among 21,853 patients, 5,879 (26.9%) were classified as early-onset colorectal cancer.
EOCRC showed higher prevalence of KRAS G12D (13.48%) and FBXW7 alterations (11.13%); both significantly differed from LOCRC (p<0.0001).
Identified genomic profiles inform targeted therapeutic strategies for EOCRC.

Abstract

e15542 Background: Colorectal cancer (CRC) diagnosed before the age of 50, referred to early-onset colorectal cancer (EOCRC), is increasing in incidence worldwide. The majority of cases are sporadic, with hereditary cancer syndromes accounting for only a small proportion. The clinical behavior and molecular characteristics of EOCRC remain incompletely characterized. This study aimed to compare the clinical and genomic features of EOCRC and late-onset colorectal cancer (LOCRC). Methods: Patients with CRC were identified from the GENIE Biopharma Collaborative (BPC) CRC v2.0 public dataset and the GENIE Cohort v18.0 public dataset, and were stratified into EOCRC and LOCRC groups based on age at the time of sequencing. Clinical and molecular characteristics were systematically analyzed. The prevalence of potentially targetable genomic alterations with FDA-approved or investigational therapies was evaluated using OncoKB, and levels of clinical actionability were assigned according to the OncoKB Therapeutic Level of Evidence (Version 2). Results: Among 21,853 patients with CRC, comprising 23,078 tumour samples, 5,879 (26.9%) were classified as EOCRC, and 14,490 (66.3%) as LOCRC. The median age at sequencing was 44 years (range, 17–50) in the EOCRC group and 64 years (range, 51–88) in the LOCRC group. Male predominance was more pronounced in the LOCRC cohort compared with the EOCRC cohort (53.8% vs. 50.5%, respectively; p 50 P-value Evidence level Therapy BRAF-V600E 201 (3.42%) 1254 (8.66%) <0.0001 1 Encorafenib + Cetuximab POLE 54 (1.16%) 43 (0.39%) 0.0001 2 Immunotherapy KRAS-G12D 792 (13.48%) 1631 (11.26%) <0.0001 3 ASP3082; MRTX-1133 KRAS-G12V 434 (7.39%) 1246 (8.60%) 0.0042 3 Daraxonrasib NF1 130 (2.64%) 238 (2.12%) 0.0419 3 Cobimetinib; Trametinib CDK12 47 (1.02%) 166 (1.58%) 0.0079 3 Immunotherapy FBXW7 648 (11.13%) 1420 (9.94%) 0.0121 4 Lunresertib + Camonsertib

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Targetable genomic alterations in early-onset colorectal cancer and their therapeutic implications: Real-world data.

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