Related Experiment Video

Updated: Jan 23, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
12:04

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

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A driving test for oncogenic mutations

David E Heppner1, Tyler S Beyett1, Michael J Eck2

  • 1From the Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.

The Journal of Biological Chemistry
|June 16, 2019
PubMed

Insights

Researchers developed a new screening method to identify cancer-driving mutations in the epidermal growth factor receptor (EGFR) kinase. This approach successfully found known mutations and a novel oncogenic EGFR mutation, A702V.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Activating mutations in protein kinases drive cancer development.
  • Identifying oncogenic driver mutations is crucial for effective cancer therapy.
  • Distinguishing driver mutations from passenger mutations is a significant challenge.

Purpose of the Study:

  • To develop and validate a screening approach for identifying gain-of-function mutations in the epidermal growth factor receptor (EGFR) kinase.
  • To discover previously uncharacterized oncogenic EGFR mutations that can be targeted by drugs.

Main Methods:

  • Utilized an error-prone PCR-based screening strategy.
  • Employed a proliferating cell model to assess kinase activity.
  • Validated the screen by identifying known cancer-promoting EGFR mutations.

Main Results:

  • The screening method successfully identified known activating EGFR mutations.
  • A novel oncogenic EGFR mutation, A702V, was discovered.
  • The approach demonstrated efficacy in discovering driver mutations.

Conclusions:

  • The developed screening approach is powerful for identifying oncogenic driver mutations.
  • This method can accelerate the discovery of new therapeutic targets in cancer.
  • The identification of EGFR A702V highlights the potential of this screen for future cancer research.

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