Analysis of driver mutations in female non-smoker Asian patients with pulmonary adenocarcinoma.
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.
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine Cancer Institute, Tongji University, No 507 Zhengmin Road, Shanghai 200433, People's Republic of China.
Shengxiang
S
Ren
Peng
P
Kuang
Limou
L
Zheng
Chunxia
C
Su
Jiayu
J
Li
Bing
B
Li
Xiaoxia
X
Chen
Yongshen
Y
Wang
V
V
KimCurran
Lu
L
Liu
Qiong
Q
Hu
Jie
J
Zhang
Liang
L
Tang
Caicun
C
Zhou
D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D044466:Asian People; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking; D018631:ras Proteins / Q000235:genetics
D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; C512478:EGFR protein, human; C482119:BRAF protein, human