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
Summary
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.
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