EGFR/KRAS mutations and gefitinib therapy in Chinese NSCLC patients.
BACKGROUND
For gefitinib treatment for non-small cell lung cancer (NSCLC), KRAS mutations reportedly behave as a resistance marker, and the epidermal growth factor receptor (EGFR) as a responsive marker. It is known that Asians and Caucasians have different responses to gefitinib. We investigated the KRAS and EGFR mutation status in a group of Chinese patients with advanced NSCLC who were treated with gefitinib after a failed chemotherapy.


METHODS
Genomic DNA extracted from tumor specimens of 24 patients with advanced NSCLC, who failed at least 1 prior platinum-based chemotherapy regimen before gefitinib treatment, was subjected to nested polymerase chain reaction (PCR) to amplify codons 12, 13, 59, and 61 of the KRAS gene and exons 18-21 of the EGFR gene for direct sequencing.


RESULTS
For the 24 patients, no KRAS gene mutation was found. 15 patients (62.5%, 15/24) harbored EGFR mutations which included deletion mutations in exon 19 and missense mutations in exon 21.


CONCLUSIONS
KRAS mutation may occur at a very low frequency in Chinese NSCLC patients regardless of pathology, smoking status, or gender. Unlike EGFR, the low incidence of KRAS mutations may undermine its role in predicting the clinical response to EGFR tyrosine kinase inhibitors.
Wang
Zhen
Z
Guangdong Provincial People's Hospital, Cancer Center, Guangdong Provincial Lung Cancer Research Institute, Guangzhou, China.
Wu
Yi Long
YL
Zhang
Guo Chun
GC
Zhou
Qing
Q
Xu
Chong Rui
CR
Guo
Ai Lin
AL
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077156:Gefitinib