Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Wei Zhang - , Bayer AG (Author)
  • Arndt A Schmitz - , Bayer AG (Author)
  • Roosa E Kallionpää - , Turku University Hospital (Author)
  • Merja Perälä - , Turku University Hospital (Author)
  • Niina Pitkänen - , Turku University Hospital (Author)
  • Mikko Tukiainen - , Turku University Hospital (Author)
  • Erika Alanne - , Turku University Hospital (Author)
  • Korinna Jöhrens - , Institute of Pathology, TUD Dresden University of Technology (Author)
  • Renate Schulze-Rath - , Bayer AG (Author)
  • Bahman Farahmand - , Bayer AG (Author)
  • Jihong Zong - , Bayer AG (Author)

Abstract

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes.

MATERIAL AND METHODS: We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis.

RESULTS: Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy.

CONCLUSION: NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.

Details

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalActa Oncologica
Volume63
Publication statusPublished - 5 Jul 2024
Peer-reviewedYes

External IDs

PubMedCentral PMC11332464
Scopus 85197814498

Keywords

Sustainable Development Goals

Keywords

  • Adolescent, Adult, Aged, Biological Specimen Banks, Carcinoma, Non-Small-Cell Lung/genetics, Child, Child, Preschool, Colorectal Neoplasms/genetics, Female, Finland/epidemiology, Gene Fusion, High-Throughput Nucleotide Sequencing, Humans, Infant, Lung Neoplasms/genetics, Male, Membrane Glycoproteins, Middle Aged, Neoplasms/genetics, Oncogene Proteins, Fusion/genetics, Receptor, trkA/genetics, Receptor, trkB/genetics, Receptor, trkC/genetics, Salivary Gland Neoplasms/genetics, Sarcoma/genetics, Young Adult