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 D Yang, Lixia Guo, Yan Asmann, Peter W. Li, Michele Erickson-Johnson, Yuta Sakai, Zhifu D Sun, Hyo Sung Jeon, Hayoung Hwang, Aaron O. Bungum, Eric Edell, Vernadette A. Simon, Karla J. Kopp, Bruce Eckloff, Andre M. Oliveira, Eric D Wieben & 6 others Marie Christine Aubry, Eunhee Yi, Dennis A Wigle, Robert B Diasio, Ping Yang, Jin Jen

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

Fingerprint

Oncogenes
Mutation
Exons
Lung Neoplasms
Neoplasms
Oncogene Fusion
RNA
Mitogen-Activated Protein Kinase Kinases
Phosphorylation
Cell Proliferation
Adenocarcinoma of lung
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Common oncogene mutations and novel SND1-BRAF transcript fusion in lung adenocarcinoma from never smokers. / Jang, Jin Sung; Lee, Adam; Li, Jun; Liyanage, Hema; Yang, Yanan D; Guo, Lixia; Asmann, Yan; Li, Peter W.; Erickson-Johnson, Michele; Sakai, Yuta; Sun, Zhifu D; Jeon, Hyo Sung; Hwang, Hayoung; Bungum, Aaron O.; Edell, Eric; Simon, Vernadette A.; Kopp, Karla J.; Eckloff, Bruce; Oliveira, Andre M.; Wieben, Eric D; Aubry, Marie Christine; Yi, Eunhee; Wigle, Dennis A; Diasio, Robert B; Yang, Ping; Jen, Jin.

In: Scientific Reports, Vol. 5, 9755, 18.05.2015.

Research output: Contribution to journalArticle

Jang, JS, Lee, A, Li, J, Liyanage, H, Yang, YD, Guo, L, Asmann, Y, Li, PW, Erickson-Johnson, M, Sakai, Y, Sun, ZD, Jeon, HS, Hwang, H, Bungum, AO, Edell, E, Simon, VA, Kopp, KJ, Eckloff, B, Oliveira, AM, Wieben, ED, Aubry, MC, Yi, E, Wigle, DA, Diasio, RB, Yang, P & Jen, J 2015, 'Common oncogene mutations and novel SND1-BRAF transcript fusion in lung adenocarcinoma from never smokers', Scientific Reports, vol. 5, 9755. https://doi.org/10.1038/srep09755
Jang, Jin Sung ; Lee, Adam ; Li, Jun ; Liyanage, Hema ; Yang, Yanan D ; Guo, Lixia ; Asmann, Yan ; Li, Peter W. ; Erickson-Johnson, Michele ; Sakai, Yuta ; Sun, Zhifu D ; Jeon, Hyo Sung ; Hwang, Hayoung ; Bungum, Aaron O. ; Edell, Eric ; Simon, Vernadette A. ; Kopp, Karla J. ; Eckloff, Bruce ; Oliveira, Andre M. ; Wieben, Eric D ; Aubry, Marie Christine ; Yi, Eunhee ; Wigle, Dennis A ; Diasio, Robert B ; Yang, Ping ; Jen, Jin. / Common oncogene mutations and novel SND1-BRAF transcript fusion in lung adenocarcinoma from never smokers. In: Scientific Reports. 2015 ; Vol. 5.
@article{687090ee68964c799e18ca26fd3ef49d,
title = "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.",
author = "Jang, {Jin Sung} and Adam Lee and Jun Li and Hema Liyanage and Yang, {Yanan D} and Lixia Guo and Yan Asmann and Li, {Peter W.} and Michele Erickson-Johnson and Yuta Sakai and Sun, {Zhifu D} and Jeon, {Hyo Sung} and Hayoung Hwang and Bungum, {Aaron O.} and Eric Edell and Simon, {Vernadette A.} and Kopp, {Karla J.} and Bruce Eckloff and Oliveira, {Andre M.} and Wieben, {Eric D} and Aubry, {Marie Christine} and Eunhee Yi and Wigle, {Dennis A} and Diasio, {Robert B} and Ping Yang and Jin Jen",
year = "2015",
month = "5",
day = "18",
doi = "10.1038/srep09755",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Common oncogene mutations and novel SND1-BRAF transcript fusion in lung adenocarcinoma from never smokers

AU - Jang, Jin Sung

AU - Lee, Adam

AU - Li, Jun

AU - Liyanage, Hema

AU - Yang, Yanan D

AU - Guo, Lixia

AU - Asmann, Yan

AU - Li, Peter W.

AU - Erickson-Johnson, Michele

AU - Sakai, Yuta

AU - Sun, Zhifu D

AU - Jeon, Hyo Sung

AU - Hwang, Hayoung

AU - Bungum, Aaron O.

AU - Edell, Eric

AU - Simon, Vernadette A.

AU - Kopp, Karla J.

AU - Eckloff, Bruce

AU - Oliveira, Andre M.

AU - Wieben, Eric D

AU - Aubry, Marie Christine

AU - Yi, Eunhee

AU - Wigle, Dennis A

AU - Diasio, Robert B

AU - Yang, Ping

AU - Jen, Jin

PY - 2015/5/18

Y1 - 2015/5/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929600898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929600898&partnerID=8YFLogxK

U2 - 10.1038/srep09755

DO - 10.1038/srep09755

M3 - Article

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 9755

ER -