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Updated: Nov 1, 2025

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

Published on: July 5, 2019

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Oncogenic signaling of RTK fusions becomes more granular

Matthew J Cuneo1, Tanja Mittag1

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Molecular Cell
|June 18, 2021
PubMed

Insights

Fusion proteins driving cancer can activate RAS signaling by forming higher-order cytoplasmic protein granules. This process is independent of lipid membranes, offering new insights into cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Chromosomal translocations create fusion proteins in various cancers.
  • These fusions often link receptor tyrosine kinase domains with unrelated oligomerization domains.

Purpose of the Study:

  • To investigate the mechanism by which cancer-associated fusion proteins activate RAS signaling.
  • To determine if higher-order protein assembly influences signaling pathways.

Main Methods:

  • The study focused on analyzing fusion proteins generated by chromosomal translocations.
  • Researchers examined the role of cytoplasmic protein granule formation in signaling activation.

Main Results:

  • Fusion proteins capable of forming higher-order cytoplasmic granules were shown to activate RAS signaling.
  • This activation occurred independently of lipid membranes, suggesting a novel mechanism.

Conclusions:

  • Higher-order assembly of fusion proteins into cytoplasmic granules is a key driver of oncogenic RAS signaling.
  • Targeting protein granule formation could represent a new therapeutic strategy for translocation-driven cancers.

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