ArticleCancer medicine2025
Tumor Mutation Burden Survey of AACR GENIE Database Revealed NTRK (NTRK+) and RET (RET+) Fusions Positive Colorectal Carcinoma (CRC) as Distinct Subsets.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Molecular landscape and biomarker associations of functionalTranslational cancer research · 2026Article
- Dissociation Between Tumor Response and PTTM Progression During Entrectinib Therapy in NTRK Fusion-Positive Colon Cancer.Current oncology (Toronto, Ont.) · 2025Article
- Agnostic Biomarkers and Molecular Signatures in Colorectal Cancer-Guiding Chemotherapy and Predicting Response.Biomedicines · 2025Review
- A Machine-Learning Prognostic Model for Colorectal Cancer Using a Complement-Related Risk Signature.Oncology research · 2025Article
- Cancer of Unknown Primary Most Suggestive of Colorectal Origin With Microsatellite Instability-high Status and High Tumor Mutation Burden Including NTRK Fusion.Cancer diagnosis & prognosisArticle
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReceptor tyrosine kinase (RTK) inhibitors have been approved for the treatment of NTRK fusion (NTRK+) and RET fusion (RET+) positive solid tumors in a tumor-agnostic manner. However, the objective response rate was the lowest among entrectinib-treated NTRK+ colorectal cancer (CRC) (20%) and selpercatinib-treated RET+ CRC (20%) among all NTRK+, and RET+ solid tumors, respectively.
methodsWe compared tumor mutation burden (TMB) in NTRK+/RET+ CRC with all other NTRK+ and RET+ solid tumors using the American Association for Cancer Research (AACR) GENIE database (Version 13.0).
resultsWe identified 14,812 unique CRC patients. Considering only samples with identified fusion partners, the mean TMB was 66.6 ± 15.8 (mt/MB) for NTRK+ CRC (N = 9) and 35 ± 11.5 for RET+ CRC (N = 4), which were significantly higher when compared to the mean number of 6.2 ± 5.4 of TMB for all other RTK+ CRC (N = 30, p < 0.05). Furthermore, NTRK+ CRC harbored significantly higher TMB than RET+ CRC (p = 0.003). In comparison, the mean TMB was 4.0 ± 1.9 for RET+ NSCLC (N = 65) and 2.6 ± 1.6 for RET+ Thyroid cancer (N = 52). Mean TMB for all other NTRK+ solid tumors was < 11 and significantly lower than the mean TMB of NTRK+ CRC. 1482 (10.0%) CRC patients had their MSI status reported. Three out of three NTRK+ CRC patients with known MSI status were all dMMR (100%). 0 out of 12 non-NTRK/non-RET RTK+ CRC patients were dMMR (0%).
conclusionsNRTK+ and RET+ CRC possess significantly higher TMB than other RTK+ CRC or NTRK+/RET+ non-CRC solid tumors. TMB testing should be routinely done in MSI-H CRC, and TMB ≥ 35 mut/MB samples should be screened for NTRK and RET fusions as an enrichment strategy to provide additional treatment for NTRK+ and RET+ CRC patients.
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