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Genetic Characteristics of Patients Who Have Solid Tumors With ALK/ROS1/NTRK Fusions

By: Emily Rhode
Posted: Thursday, August 25, 2022

Professor Yi Sun, of The Second Xiangya Hospital, Central South University, Changsha, China, and colleagues conducted a study to characterize the genomic features of patients who have solid tumors harboring receptor tyrosine kinase (RTK) fusions involving ALK, ROS1, and NTRK. Their findings, which were published in the journal Frontiers in Oncology, may offer genomic information for the personalized clinical management of such patients.

“The gene-intergenic fusion and the fusion with rare formation directions accounted for a certain proportion in all samples, and 62 novel fusions were discovered,” the investigators commented.

Next-generation sequencing genomic data from 7,537 samples from Chinese patients with solid tumors were obtained and compared with data from 10,945 samples collected from patients in the Memorial Sloan Kettering Cancer Center (MSK) database. The researchers evaluated the association of ALK, ROS1, and NTRK fusions with age, gender, and cancer types.

A total of 180 Chinese patients with solid tumors and 121 patients in the MSK database were found to have ALK/ROS1/NTRK fusion–positive tumors. Based on their statistical analysis, the researchers found that 1.4% of patients harbored ALK rearrangements, 0.5% of patients harbored ROS1 rearrangements, and 0.5% harbored NTRK fusions. These fusions were found to be more common in younger female patients (P < .001) and had a greater expression of PD-L1. The frequency of copy number variations found in ALK/ROS1/NTRK fusion–positive samples was associated with a poor prognosis (P = .01), the investigators reported.

RTK fusions (including ALK, ROS1, and NTRK) exhibited a higher PD-L1 expression than RTK fusion–negative tumors (P < .0001), with the highest expression exhibited in tumors with ALK (P = .0484); according to investigators, this finding may offer predictive values for the benefits of immune checkpoint inhibitors in the treatment of solid tumors. The researchers also noted that 7% of the Chinese patients with RTK fusion–positive tumors carried the pathogenic IL-7R copy number variation compared with 0% of the MSK cohort.

Disclosure: For a full list of authors’ disclosures, visit frontiersin.org.


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