title: Epidermal growth factor receptor exon 20 mutation increased in post-chemotherapy patients with non-small cell lung cancer detected with patients' blood samples.
abstract: OBJECTIVE
  Patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR)-mutations have excellent response to EGFR tyrosine kinase inhibitors (TKIs), and exon 20 mutation accounts for most of TKI drug resistance. Nested polymerase chain reaction (PCR) was used to detect EGFR exon 20 mutations of patients with NSCLC after chemotherapy. The same is being analyzed with patients' characteristics.
  
  
  METHODS
  Peripheral blood samples were collected from 273 patients with NSCLC, including 143 with adenocarcinoma (ADC) and 130 with squamous cell carcinoma (SCC), after chemotherapy. DNA was extracted from whole blood for nested PCR amplification and purification. Sequencing was carried out in an automated 3730 sequencer, followed by analysis of EGFR exon 20 mutations from nested PCR products.
  
  
  RESULTS
  The mutations of EGFR exon 20 were mainly point mutations in rs1050171 (c.2361A>G) and rs56183713 (c.2457G>A). The point mutation was 28.21%, 28.46%, and 27.97% in patients with NSCLC, ADC and SCC, respectively. Men had an equivalent mutation (27.18%) to women (30.77%). The mutation in smokers and nonsmokers was 27.68% and 29.17%, respectively. In unselected patients, there was no correlation between EGFR exon 20 mutations and patients' characteristics of age, gender, smoking history, histologic type, or tumor-node-metastasis (TNM) staging system. In subgroup analyses, the EGFR mutation of patients with SCC was correlated with TNM stage [P = .013; odds ratio = 1.758; 95% confidence interval (CI) = 1.125-2.747].
  
  
  CONCLUSIONS
  The data indicate that the chemotherapy may induce EGFR-TKI-resistant mutation in NSCLC cells and EGFR-TKI should be used in the early stage of NSCLC but not after chemotherapy.
authors.affiliation: Department of Basic Medical Science, Zhejiang Chinese Medical University. Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenlong
authors.initials: W
authors.lastname: Bao
authors.forename: Hua
authors.initials: H
authors.lastname: Shi
authors.forename: Chuming
authors.initials: C
authors.lastname: Jiang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhang
references.citation: J Thorac Oncol. 2006 Oct;1(8):847-55
references.pmid: 17409969
references.citation: JAMA. 2003 Oct 22;290(16):2149-58
references.pmid: 14570950
references.citation: J Thorac Oncol. 2007 May;2(5):430-9
references.pmid: 17473659
references.citation: Nat Rev Cancer. 2010 Nov;10(11):760-74
references.pmid: 20966921
references.citation: J Clin Oncol. 2009 Jun 1;27(16):2653-9
references.pmid: 19414683
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11
references.pmid: 15329413
references.citation: Clin Cancer Res. 2011 Mar 15;17(6):1616-22
references.pmid: 21135146
references.citation: J Clin Oncol. 2004 Mar 15;22(6):1103-9
references.pmid: 15020612
references.citation: Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37
references.pmid: 16257339
references.citation: J Clin Oncol. 2005 Feb 1;23(4):857-65
references.pmid: 15681531
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8195-203
references.pmid: 15623594
references.citation: Cancer Res. 2004 Dec 15;64(24):8919-23
references.pmid: 15604253
references.citation: J Clin Oncol. 2006 Aug 20;24(24):3831-7
references.pmid: 16921034
references.citation: Lancet Oncol. 2012 Mar;13(3):239-46
references.pmid: 22285168
references.citation: Clin Cancer Res. 2005 Feb 1;11(3):1167-73
references.pmid: 15709185
references.citation: N Engl J Med. 2009 Sep 3;361(10):947-57
references.pmid: 19692680
references.citation: Lung Cancer. 2010 May;68(2):198-203
references.pmid: 19589612
references.citation: J Clin Oncol. 2002 Sep 15;20(18):3815-25
references.pmid: 12228201
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2493-501
references.pmid: 15710947
references.citation: Clin Cancer Res. 2011 Mar 1;17(5):1160-8
references.pmid: 21233402
references.citation: J Clin Oncol. 2003 Jul 15;21(14):2787-99
references.pmid: 12860957
references.citation: Clin Cancer Res. 2006 Oct 1;12(19):5764-9
references.pmid: 17020982
references.citation: Zhongguo Fei Ai Za Zhi. 2011 Feb;14(2):127-31
references.pmid: 21342642
references.citation: N Engl J Med. 2010 Jun 24;362(25):2380-8
references.pmid: 20573926
references.citation: J Clin Oncol. 2002 Nov 1;20(21):4292-302
references.pmid: 12409327
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2237-46
references.pmid: 12748244
references.citation: Cancer Res. 2006 Aug 15;66(16):7854-8
references.pmid: 16912157
references.citation: Lancet Oncol. 2009 May;10(5):432-3
references.pmid: 19410185
references.citation: Lancet Oncol. 2011 Aug;12(8):735-42
references.pmid: 21783417
references.citation: J Natl Compr Canc Netw. 2012 Mar;10(3):292-5
references.pmid: 22393190
references.citation: Lancet Oncol. 2010 Feb;11(2):121-8
references.pmid: 20022809
references.citation: J Clin Oncol. 2008 May 20;26(15):2442-9
references.pmid: 18458038
references.citation: J Clin Oncol. 2012 Feb 1;30(4):433-40
references.pmid: 22215752
references.citation: Clin Cancer Res. 2006 Dec 15;12(24):7232-41
references.pmid: 17189394
references.citation: N Engl J Med. 2008 Jul 24;359(4):366-77
references.pmid: 18596266
references.citation: PLoS Med. 2005 Mar;2(3):e73
references.pmid: 15737014
references.citation: J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
references.pmid: 15741570
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Ann Oncol. 2004 May;15(5):831-8
references.pmid: 15111354