Skip Navigation LinksHome > January 2014 - Volume 9 - Issue 1 > RET Rearrangements in Lung Adenocarcinoma and Radiation
Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000015
Brief Reports

RET Rearrangements in Lung Adenocarcinoma and Radiation

Dacic, Sanja MD, PhD*; Luvison, Alyssa BS*; Evdokimova, Viktoria PhD*; Kelly, Lindsey BS*; Siegfried, Jill M. PhD; Villaruz, Liza C. MD; Socinski, Mark A. MD; Nikiforov, Yuri E. MD, PhD*

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Abstract

Background:

RET rearrangement, a hallmark of radiation-induced thyroid cancer, has been reported to occur in 1% of lung adenocarcinoma patients. Patients with this rearrangement tend to be younger and never smokers, raising a possibility of other causes, such as radiation. We hypothesized that RET chromosomal rearrangement may represent a genetic mechanism of radiation-induced lung cancer.

Methods:

Two hundred forty-five consecutive primary lung adenocarcinomas without history of radiation and 38 lung adenocarcinoma patients with a history of therapeutic radiation for breast carcinoma or mediastinal Hodkgin lymphoma were tested for RET rearrangement by fluorescence in situ hybridization. Human lung adenocarcinoma cells (201T) were subjected to γ radiation and tested for RET gene fusions by reverse transcriptase-polymerase chain reaction and Southern blot hybridization.

Results:

We identified one case with RET rearrangement in the group without history of radiation (1 of 240; 0.4%) and two cases in the group with history of radiation (2 of 37; 5.4%; P=0.0436). Both these patients were women, who were former smokers with a history of breast carcinoma treated with surgery and radiation. Furthermore, we found that RET fusions could be directly induced in 201T human lung cells by exposure to 1 Gy of γ radiation. All fusions identified were between RET and KIF5B genes, and no RET fusions to CCDC6 or NCOA4 genes, characteristic for thyroid cancer, were identified in the irradiated lung cells.

Conclusion:

RET fusions may represent a genetic mechanism of radiation-induced lung adenocarcinoma.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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