Analysis of driver mutations in female non-smoker Asian patients with pulmonary adenocarcinoma

Cell Biochem Biophys. 2012 Nov;64(2):155-60. doi: 10.1007/s12013-012-9384-8.


Previous studies have revealed that EGFR mutation and/or EML4-ALK gene fusion rate was higher in the non-smoker Asian females with pulmonary adenocarcinoma. The aim of this study is to determine the distribution of known oncogenic driver mutations in the female non-smoker Asian patients with pulmonary adenocarcinoma. 104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA. 73 (70.2 %) tumors harbored EGFR mutations; among these, 28 were deletions in exon 19, 44 were L858R missense changes, and eight were T790M mutations. 10 (9.6 %) harbored EML4-ALK fusions, two harbored KRAS mutations, two harbored BRAF mutations, and two harbored PI3K mutations. A majority of the mutations were mutually exclusive, except two with EGFR mutation and BRAF mutation, one with EML4-ALK fusions and PI3K mutation. Thus, 82.7 % (86 of 104; 95 % CI, 75.4-90.0 %) of lung adenocarcinomas from non-smoker females were found to harbor the well-known oncogenic mutations in five genes. Lung cancer in non-smoking Asian females is a distinct entity, with majority of this subgroup being developed by the oncogenic mutations. The prospective mutation examination in this population will be helpful for devising a targeted therapy for a majority of the patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Asian People*
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • Exons
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Smoking
  • ras Proteins / genetics


  • EML4-ALK fusion protein, human
  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • EGFR protein, human
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins