RET rearrangements in lung adenocarcinoma and radiation

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)118-120
Number of pages3
JournalJournal of Thoracic Oncology
Volume9
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Lung adenocarcinoma
  • RET proto oncogene
  • Radiation

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