Common oncogene mutations and novel SND1-BRAF transcript fusion in lung adenocarcinoma from never smokers

Jin Sung Jang, Adam Lee, Jun Li, Hema Liyanage, Yanan Yang, Lixia Guo, Yan W. Asmann, Peter W. Li, Michele Erickson-Johnson, Yuta Sakai, Zhi Fu Sun, Hyo Sung Jeon, Hayoung Hwang, Aaron O. Bungum, Eric S. Edell, Vernadette A. Simon, Karla J. Kopp, Bruce Eckloff, Andre M. Oliveira, Eric WiebenMarie Christine Aubry, Eunhee Yi, Dennis Wigle, Robert B. Diasio, Ping Yang, Jin Jen

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Lung adenocarcinomas from never smokers account for approximately 15 to 20% of all lung cancers and these tumors often carry genetic alterations that are responsive to targeted therapy. Here we examined mutation status in 10 oncogenes among 89 lung adenocarcinomas from never smokers. We also screened for oncogene fusion transcripts in 20 of the 89 tumors by RNA-Seq. In total, 62 tumors had mutations in at least one of the 10 oncogenes, including EGFR (49 cases, 55%), K-ras (5 cases, 6%), BRAF (4 cases, 5%), PIK3CA (3 cases, 3%), and ERBB2 (4 cases, 5%). In addition to ALK fusions identified by IHC/FISH in four cases, two previously known fusions involving EZR-ROS1 and KIF5B-RET were identified by RNA-Seq as well as a third novel fusion transcript that was formed between exons 1-9 of SND1 and exons 2 to 3′ end of BRAF. This in-frame fusion was observed in 3/89 tested tumors and 2/64 additional never smoker lung adenocarcinoma samples. Ectopic expression of SND1-BRAF in H1299 cells increased phosphorylation levels of MEK/ERK, cell proliferation, and spheroid formation compared to parental mock-transfected control. Jointly, our results suggest a potential role of the novel BRAF fusion in lung cancer development and therapy.

Original languageEnglish (US)
Article number9755
JournalScientific reports
Volume5
DOIs
StatePublished - May 18 2015

ASJC Scopus subject areas

  • General

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