Spectrum of LKB1, EGFR, and KRAS Mutations in Chinese Lung Adenocarcinomas

Abstract

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.

NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition

“…8,27,28 Recent co-clinical trial study has shown that LKB1-deficient lung tumors are intrinsically resistant to multiple drug treatments, 29 highlighting that this subset of lung cancer may represent as a unique subpopulation. Our studies in de novo mouse models have previously shown that LKB1-deficient metastatic lung tumors display an EMT pattern.…”

Establishment and characterization of primary lung cancer cell lines from Chinese population

“…Detection of EGFR and KRAS mutations was previously described [18,21] . Briefly, genomic DNA and RNA were extracted from Chinese lung cancer cell lines per standard protocol (RNeasy Mini Kit, and QIAamp DNA Mini Kit, Qiagen, Hilden, Germany).…”

“…Total RNA was reverse transcribed into single-stranded cDNA using a RevertAid™ First Strand cDNA Synthesis Kit (Fermentas, EU, USA) and sequenced. The cDNA regions of EGFR (exons [18][19][20][21][22] and KRAS (exons 2-3) were then PCR amplified and sequenced. All mutations found from the cDNA sequencing were further confirmed by genomic DNA sequencing.…”

“…Studies demonstrate that ethnic differences in genetic background are important in defining cancer biology as well as in drug toxicity [14][15][16][17][18][19][20][21] . For example, the epidermal growth factor receptor (EGFR) kinase domain mutations occur in approximately 10% of NSCLC patients in the Caucasian popula tion [22] , but occur in 30%-50% of NSCLC patients from East Asian populations [15,17,18,21,23] .…”

“…For example, the epidermal growth factor receptor (EGFR) kinase domain mutations occur in approximately 10% of NSCLC patients in the Caucasian popula tion [22] , but occur in 30%-50% of NSCLC patients from East Asian populations [15,17,18,21,23] . Ethnic differences in the expression of allelic variants may produce altered pharmacokinetics and Establishment and characterization of primary lung cancer cell lines from Chinese population www.nature.com/aps Zheng C et al Acta Pharmacologica Sinica npg result in differential toxicity for the same anticancer treatments [19,20] .…”