NTRK fusion in Japanese colorectal adenocarcinomas

Sci Rep. 2021 Mar 11;11(1):5635. doi: 10.1038/s41598-021-85075-y.

Abstract

NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Asian People*
  • Base Sequence
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Japan
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Receptor, trkA / genetics*
  • Sequence Analysis, RNA

Substances

  • Oncogene Proteins, Fusion
  • Receptor, trkA