Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 5, Issue 8, Pages 1130-1135Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0b013e3181e05016
Keywords
Chinese lung adenocarcinoma; LKB1; EGFR; KRAS; Mutation
Categories
Funding
- National Basic Research Program of China [2010CB912102]
- National Natural Science Foundation of China [30623003, 30740084, 30871284]
- Chinese Academy of Sciences [2008KIP101, KSCX1-YW-22]
- Science and Technology Commission of Shanghai Municipality [08PJ14105, 09JC1416300]
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Introduction: Somatic LKB1 mutations are found in lung adenocarcinomas at different frequencies in Caucasian and East Asian (Japanese and Korean) populations. This study was designed to characterize the frequency of LKB1 mutations, their relationship to EGFR and KRAS mutations, and their associated clinicopathologic characteristics in Chinese patients. Methods: Two hundred thirty-nine lung adenocarcinomas consecutively collected from October 2007 to July 2009 were dissected into 3 to 4 small (3 mm) pieces for histopathological analyses of tumor content. Genomic DNA and/or cDNA from 86 samples with more than 70% tumor content were used for sequencing of LKB1 (exons 1-9), EGFR (exons 18-21), and KRAS (exon 2). LKB1 germline mutation status was determined by sequencing of genomic DNA from matched histologically distant lung tissues that are histologically normal. Results: 6.9% of lung adenocarcinomas harbored LKB1 somatic mutations. A total of 10.5% of patients had an LKB1 germline polymorphism, F354L. Interestingly, in two of these patients, tumors displayed loss of heterozygosity at this allele. EGFR kinase domain and KRAS mutations were found in 66.3% and 2.3% of Chinese lung adenocarcinomas, respectively. Concurrent LKB1 and EGFR somatic mutations were observed in one patient. Both KRAS-mutant tumors harbored LKB1 mutations. Conclusions: These data provide important clinical and molecular characteristics of lung adenocarcinomas from Chinese patients.
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