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Keap1 mutations in lung cancer patients

Hidefumi Sasaki1, Ayumi Suzuki, Masayuki Shitara

  • 1Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.

Oncology Letters
|October 19, 2013
PubMed

Insights

Kelch-like ECH-associated protein 1 (Keap1) mutations were found in 2.6% of lung adenocarcinoma patients. These Keap1 mutations occurred exclusively with other gene mutations, suggesting potential for personalized lung cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Kelch-like ECH-associated protein 1 (Keap1) is a tumor suppressor candidate that regulates nuclear factor erythroid 2-related 2 (NRF2).
  • Previous research identified somatic mutations in the NRF2 gene (NFE2L2), but the clinical significance of Keap1 mutations in lung cancer remains unclear.

Purpose of the Study:

  • To investigate the mutational status of Keap1 in non-small cell lung cancer (NSCLC).
  • To explore the correlation between Keap1 mutations and clinicopathological features in lung cancer patients.

Main Methods:

  • Reverse transcription PCR and direct sequencing were used to analyze Keap1 mutational status.
  • Study included 76 surgically removed lung cancer cases with pre-established EGFR and NFE2L2 mutation data.

Main Results:

  • Keap1 mutations were identified in 2 (2.6%) cases of adenocarcinoma, both from heavy smokers.
  • Keap1 mutations were exclusively found in advanced adenocarcinoma (4.3%) and did not co-occur with EGFR, KRAS, ERBB2, or NRF2L2 mutations.

Conclusions:

  • Keap1 mutations are rare in NSCLC but exclusively associated with specific subtypes and smoking history.
  • The exclusive nature of Keap1 mutations may aid in selecting personalized therapeutic strategies for lung cancer.
Keywords:
Keap1NRF2adenocarcinomalung cancermutations

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