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Updated: Sep 5, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

9.7K

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

Yinghuan Dai1, Ping Liu2, Wenlong He3

  • 1Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Oncology
|July 5, 2022
PubMed

Insights

Receptor tyrosine kinase fusions involving anaplastic lymphoma kinase (ALK), ROS1, and NTRK are common in younger females with solid tumors. These fusions, along with genetic alterations, impact patient survival and inform precision medicine strategies.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Receptor tyrosine kinase (RTK) fusions, including anaplastic lymphoma kinase (ALK), ROS1, and neurotrophic receptor tyrosine kinase (NTRK), are key therapeutic targets in various solid tumors.
  • Understanding the genomic landscape of these fusions is crucial for advancing precision medicine.

Purpose of the Study:

  • To comprehensively characterize the genomic features of solid tumor patients with ALK, ROS1, and NTRK fusions.
  • To compare these features with an external cohort and identify novel fusions and associated genetic alterations.
  • To explore the clinical implications of these genomic findings on patient survival and treatment strategies.

Main Methods:

  • Next-generation sequencing (NGS) was employed to analyze the genomic profiles of 180 Chinese solid tumor patients.
  • Data from 121 patients in the Memorial Sloan Kettering Cancer Center (MSKCC) database were used for comparative analysis.
  • Mutational signatures, copy number variations (CNVs), and differentially mutated genes were identified.

Main Results:

  • ALK, ROS1, and NTRK fusions were more prevalent in younger female patients and associated with higher programmed death ligand 1 (PD-L1) expression.
  • Sixty-two novel fusions were discovered, with gene-intergenic and rare formation directions present.
  • TP53 and MUC16 alterations were common; patients with fusions and CNVs exhibited shorter overall survival in the MSKCC cohort.
  • MAPK signaling and FOXO signaling pathways were differentially regulated between fusion-positive and -negative patients.

Conclusions:

  • Genomic characterization reveals distinct features of RTK fusions in solid tumors, particularly in younger females.
  • The discovery of novel fusions and associated alterations provides valuable insights for targeted therapies.
  • These findings support the integration of genomic data for personalized clinical management in the era of precision medicine.
Keywords:
ALKNTRKROS1copy number variantsgene fusionmutational signaturenext generation sequencingprogrammed death ligand 1

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