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Sci Rep. 2015 May 18;5:9755. doi: 10.1038/srep09755.

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

Author information

1
Departments of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
2
Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
3
Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Jilin, China.
4
Sequenom, Inc., San Diego, CA, USA.
5
Health Science Research, Mayo Clinic, Rochester, MN.
6
Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
7
Molecular Diagnostics and Imaging Center, School of Medicine, Kyungpook National University, Daegu, Korea.
8
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.
9
Gene Expression Core, Mayo Clinic, Rochester, MN.
10
Biospecimen Accessioning and Processing Core, Mayo Clinic, Rochester, MN.
11
DNA Sequencing Core, Mayo Clinic, Rochester, MN.
12
Thoracic Surgery, Mayo Clinic, Rochester, MN.

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.

PMID:
25985019
PMCID:
PMC4434945
DOI:
10.1038/srep09755
[Indexed for MEDLINE]
Free PMC Article

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