MEK1 and AKT2 mutations in Japanese lung cancer

Hidefumi Sasaki1, Yu Hikosaka, Osamu Kawano

  • 1Department of Oncology, Immunology and Surgery II, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp

Abstract

Insights

MEK1 and AKT2 gene mutations are rare in non-small cell lung cancer. AKT2 mutations co-occurred with EGFR and PIK3CA mutations, unlike MEK1 mutations which were exclusive.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Somatic mutations in the epidermal growth factor receptor (EGFR) signaling pathway are implicated in non-small cell lung cancer (NSCLC).
  • Previous reports identified MEK1 gene mutations in exon 2 and AKT2 (v-akt murine thymoma viral oncogene homologue 2) gene mutations in the kinase domain in NSCLC.

Purpose of the Study:

  • To investigate the frequency and co-occurrence patterns of MEK1 and AKT2 mutations in surgically treated NSCLC.
  • To analyze MEK1 exon 2 and AKT2 kinase domain mutations in a cohort of Japanese lung cancer patients.

Main Methods:

  • Direct sequencing was used to analyze MEK1 (n=280) and AKT2 (n=273) mutations in NSCLC patient samples.
  • Mutation status of MEK1 (exon 2) and AKT2 (kinase domain) was determined for each case.

Main Results:

  • MEK1 mutation (K57K) was detected in 1 out of 280 (0.4%) NSCLC patients.
  • AKT2 mutation (R371H) was found in 1 out of 273 (0.4%) NSCLC patients.
  • MEK1 mutations were mutually exclusive with EGFR, K-ras, and B-raf mutations, while AKT2 mutations coexisted with EGFR and PIK3CA mutations.

Conclusions:

  • Mutations in the kinase domain of AKT2 and MEK1 exon 2 occur infrequently in Japanese NSCLC.
  • The distinct co-mutation profiles of MEK1 and AKT2 suggest different roles in NSCLC pathogenesis.

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