Common Oncogene Mutations and Novel SND1-BRAF Transcript Fusion in Lung Adenocarcinoma from Never Smokers.

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.

• Authors: Jin Sung Jang, Adam Lee, Jun Li, Hema Liyanage, Yanan Yang, Lixia Guo, Yan W Asmann, Peter W Li, Michele Erickson-Johnson, Yuta Sakai, ZhiFu Sun, Hyo-Sung Jeon, Hayoung Hwang, Aaron O Bungum, Eric S Edell, Vernadette A Simon, Karla J Kopp, Bruce Eckloff, Andre M Oliveira, Eric Wieben, Marie Christine Aubry, Eunhee Yi, Dennis Wigle, Robert B Diasio, Ping Yang, Jin Jen
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 9755 (May 18 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25985019 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Nuclear Proteins
• Oncogene Proteins, Fusion
• Proto-Oncogene Proteins B-raf
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases
• Endonucleases
• SND1 protein, human

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Adenocarcinoma of Lung
• Aged
• Aged, 80 and over
• Biomarkers, Tumor
• Endonucleases
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Gene Order
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Mitogen-Activated Protein Kinases (metabolism)
• Mutation
• Neoplasm Staging
• Nuclear Proteins (genetics, metabolism)
• Oncogene Proteins, Fusion (genetics, metabolism)
• Oncogenes
• Phosphorylation
• Proto-Oncogene Proteins B-raf (genetics, metabolism)
• Reproducibility of Results
• Transcription, Genetic