Open AccessNTRK fusion positive colorectal cancer is a unique subset of CRC with high TMB and microsatellite instability
Author(s) -
Wang Hui,
Li ZhiWei,
Ou Qiuxiang,
Wu Xue,
Nagasaka Misako,
Shao Yang,
Ou SaiHong Ignatius,
Yang Yu
Publication year - 2022
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.4561
Subject(s) - microsatellite instability , colorectal cancer , cancer research , population , cancer , medicine , trk receptor , fusion gene , oncology , biology , gene , receptor , microsatellite , genetics , allele , environmental health , neurotrophin
Abstract TRK fusions are rare but targetable mutations which occur across a wide variety of cancer types. We report the prevalence of approximately 0.7% for NTRK ‐positive colorectal cancer (CRC) by genetically profiling 2519 colonic and rectal tumors. The aberrations of APC and TP53 frequently co‐occurred with NTRK gene fusions, whereas RAS/BRAF oncogenic alterations and NTRK fusions were almost always mutually exclusive. NTRK ‐driven colorectal cancer patients demonstrated increased TMB (median = 53 mut/MB, 95% CI: 36.8–68.0 mut/MB), high microsatellite instability, and an enrichment for POLE/POLD1 mutations when compared to molecularly unstratified colorectal cancer population. These data shed light on possible future approach of multimodality treatment regimen including TRK‐targeted therapy and immune checkpoint inhibitor therapy in NTRK ‐positive CRCs.