Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer.

BACKGROUND

The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.

METHODS

This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.

RESULTS

Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, <0.001), wildtype (2.0% vs. 0.2%, <0.001) and mutation (7.7% vs. 0.4%, <0.001) than in patients with microsatellite stability/MSI-low, mutation and wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases.

CONCLUSIONS

Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving . Actionable gene fusions are more prevalent in MSI-H, wildtype, or -mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.