Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma

Cancer Biology & Therapy
Eun Young KimYoon Soo Chang

Abstract

Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotin...Continue Reading

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Citations

Oct 21, 2016·Scientific Reports·Yi ShiZe-Guang Han
May 5, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shaohua Cui, Liyan Jiang
Dec 12, 2018·Current Cancer Drug Targets·Tatsuya NaganoYoshihiro Nishimura
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Jan 5, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Takeshi HiroseShinji Kohsaka
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Jan 14, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·James Chih-Hsin YangEdward S Kim
Apr 3, 2021·Journal of Cancer Research and Clinical Oncology·Daisuke UedaMorihito Okada
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Dec 10, 2021·Molecular and Clinical Oncology·Taisuke MatsubaraNorihiko Ikeda

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Methods Mentioned

BETA
genotyping
surgical resection
Chip
PCR
chips

Software Mentioned

Bam
SPSS Statistics
Ion Torrent Suite
tmap
Ion Torrent Variant Caller ( ITVC )
BioAnalyzer
Ion Torrent

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