EGFR mutation L747P led to gefitinib resistance and accelerated liver metastases in a Chinese patient with lung adenocarcinoma.
BACKGROUND
Mutations in the epidermal growth factor receptor gene (EGFR) are found in around half of Asian patients with non-small cell lung cancer (NSCLC). For this reason, EGFR tyrosine kinase inhibitors (TKI) are often prescribed depending on the EGFR status. Two common EGFR mutations, a deletion in exon 19 and L858R in exon 21, demonstrate a positive response to gefitinib, the first approved EGFR TKI. However, T790M and an insertion in EGFR exon 21 are resistant to EGFR TKI treatment. The relationships between the EGFR mutation type and response to the target drug have not been fully investigated.


METHODS
We describe a 66-year-old Chinese male diagnosed with stage IV lung adenocarcinoma based on evidence from a computed tomography (CT) scan and histological features of a biopsy taken during fiberoptic bronchoscopy surgery. Molecular analysis of EGFR exons 19 and 21 revealed the presence of only one mutation in exon 19: L747P (2239-2240 TT>CC). The patient requested gefitinib treatment for 2 weeks but his response was poor. A CT scan revealed that the number and relative volume of the liver metastases had increased after treatment.


CONCLUSIONS
L747P (2239-2240 TT>CC) in exon 19 is a rare EGFR mutation that appears to lead to gefitinib resistance and might accelerate liver metastases.
Affiliated Yantai Yuhuangding Hospital, Medical College of Qingdao University Yantai 264000, China.
Guohua
G
Yu
Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University Yantai 264005, China.
Xiaoxia
X
Xie
Affiliated Yantai Yuhuangding Hospital, Medical College of Qingdao University Yantai 264000, China.
Dengjun
D
Sun
Department of Imaging Center, Affiliated Yantai Hospital of Binzhou Medical University Yantai 264100, China.
Junzu
J
Geng
Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University Yantai 264005, China.
Fenghua
F
Fu
Affiliated Yantai Yuhuangding Hospital, Medical College of Qingdao University Yantai 264000, China.
Liangming
L
Zhang
Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University Yantai 264005, China.
Hongbo
H
Wang
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D017024:Chemotherapy, Adjuvant; D002681:China; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D000077156:Gefitinib; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
EGFR; L747P; drug resistance; gefitinib; liver metastases