Closer Look at NTRK Gene Fusions in Chinese Patients With Colorectal Cancer
Posted: Sunday, August 1, 2021
Hui Wang, PhD, of the Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, and colleagues conducted a study to identify the clinicopathologic and genetic features and frequency of NTRK-driven colorectal cancers. Presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, their research showed that NTRK-positive tumors demonstrated a higher frequency of microsatellite instability, increased tumor mutation burden, and enrichment of POLE/POLD1 mutations (Abstract 3544).
The investigators focused on 2,519 unique cases of colorectal cancer in Chinese patients, retrospectively reviewing rectal and colonic tumor DNA specimens from those submitted for molecular profiling. Hybridization-based targeted next-generation sequencing was used to detect NTRK1/2/3 gene fusions. Participant demographics such as treatment history and clinical characteristics were obtained from the database.
A total of 17 NTRK-positive fusion events were identified, including 14 NTRK1-positive and 3 NTRK3-positive fusions. Of note, 13 (76%) of these NTRK-positive tumors were microsatellite instability–high tumors; this rate was much higher than that in patients with colorectal cancer who were molecularly unselected (8%) or had NTRK-positive, non-colorectal cancer tumors (< 1%).
An increased tumor mutation burden of 65 mut/MB was also observed in these patients, as patients with non–NTRK-positive colorectal cancer and non-colorectal cancer had median tumor mutation burdens of 7.7 mut/MB and 4 mut/MB, respectively. Enrichment of POLE/POLD1 mutations was discovered in 47% of patients with NTRK-positive colorectal cancer, compared with 8% of unstratified patients.
The most common fusion partner of NTRK1 was TPM3 (78%), followed by genes LMNA and TRP. A total of three NTRK3-positive colorectal cancers were discovered, and RNF43 was the most frequently mutated gene (71%). Variants of ARID1 and RNF43 were observed to be significantly enriched in microsatellite instability–positive, NTRK-positive tumors. Notably, TP53 (53%) and APC (35%) aberrations commonly co-occurred with NTRK fusions, although most of the NTRK-positive cohort was RAS/BRAF wild-type.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.