AUTHOR=Dai Yinghuan , Liu Ping , He Wenlong , Yang Lizhen , Ni Yang , Ma Xuejiao , Du Furong , Song Chao , Liu Yang , Sun Yi 

TITLE=Genomic Features of Solid Tumor Patients Harboring ALK/ROS1/NTRK Gene Fusions

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.813158

DOI=10.3389/fonc.2022.813158

ISSN=2234-943X

ABSTRACT=<p>The fusions of receptor tyrosine kinase (RTK) involving anaplastic lymphoma kinase (<italic>ALK</italic>), c-ros oncogene 1 (<italic>ROS1</italic>), and neurotrophic receptor tyrosine kinase (<italic>NTRK</italic>) represent the potential targets of therapeutic intervention for various types of solid tumors. Here, the genomic features of 180 Chinese solid tumor patients with <italic>ALK</italic>, <italic>ROS1</italic>, and <italic>NTRK</italic> fusions by next generation sequencing (NGS) were comprehensively characterized, and the data from 121 patients in Memorial Sloan Kettering Cancer Center (MSKCC) database were used to compare. We found that <italic>ALK</italic>, <italic>ROS1</italic>, and <italic>NTRK</italic> fusions were more common in younger female patients (<italic>p</italic>&lt;0.001) and showed a higher expression of programmed death ligand 1 (PD-L1). 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. Alterations in <italic>TP53</italic> and <italic>MUC16</italic> were common in patients with RTK fusions. The mutational signatures of patients were mainly distributed in COSMIC signature 1, 2, 3, 15 and 30, while had a higher frequency in copy number variations (CNVs) of individual genes, such as <italic>IL-7R</italic>. In the MSKCC cohort, patients with fusions and CNVs showed shorter overall survival than those with only fusions. Furthermore, the differentially mutated genes between fusion-positive and -negative patients mainly concentrated on MAPK signaling and FOXO signaling pathways. These results may provide genomic information for the personalized clinical management of solid tumor patients with <italic>ALK</italic>, <italic>ROS1</italic>, and <italic>NTRK</italic> fusions in the era of precision medicine.</p>