RT Journal Article
SR Electronic
T1 Identification of Genomic Alterations Acquired During Treatment With EGFR-TKIs in Non-small Cell Lung Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 671
OP 677
DO 10.21873/anticanres.13162
VO 39
IS 2
A1 NAOKI KUBO
A1 TAISHI HARADA
A1 YOSHIMASA SHIRAISHI
A1 KANAME NOSAKI
A1 NORIAKI NAKAGAKI
A1 MASAFUMI TAKESHITA
A1 HIROSHI OUCHI
A1 EIJI IWAMA
A1 KENTARO TANAKA
A1 ISAMU OKAMOTO
A1 HIROYUKI SASAKI
A1 YOICHI NAKANISHI
YR 2019
UL http://ar.iiarjournals.org/content/39/2/671.abstract
AB Background/Aim: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. Materials and Methods: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. Results: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.