Related Experiment Video

Updated: Feb 2, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
09:16

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

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SMAD4 Mutation in Small Cell Transformation of Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma

Nicky D'Haene1, Marie Le Mercier2, Isabelle Salmon2

  • 1Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium nicky.d.haene@erasme.ulb.ac.be.

The Oncologist
|November 11, 2018
PubMed

Insights

A rare epidermal growth factor receptor (EGFR) exon 18 mutation showed sensitivity to afatinib. Tumor progression revealed small cell lung cancer transformation and a SMAD4 mutation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Screening of epidermal growth factor receptor (EGFR) exons 18-21 can identify rare mutations.
  • The clinical significance and treatment sensitivity of these atypical alterations are often uncertain.

Observation:

  • A rare exon 18 EGFR mutation (p.E709_710 > D) was identified.
  • This mutation conferred sensitivity to the second-generation EGFR tyrosine kinase inhibitor (TKI) afatinib, lasting for one year.

Findings:

  • Tumor progression biopsy revealed a transformation to small cell lung cancer.
  • A SMAD4 mutation was acquired concurrently with the small cell transformation.

Implications:

  • This case highlights a rare EGFR mutation responsive to afatinib.
  • It also demonstrates a potential mechanism of acquired resistance involving tumor transformation and SMAD4 mutation in EGFR-mutated lung cancer.

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