title: RET rearrangements in lung adenocarcinoma and radiation.
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.
  
  
  CONCLUSIONS
  RET fusions may represent a genetic mechanism of radiation-induced lung adenocarcinoma.
authors.affiliation: Departments of *Pathology, †Pharmacology, University of Pittsburgh; and 3University of Pittsburgh Cancer Institute, University of Pittsburgh, School of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania.
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: Alyssa
authors.initials: A
authors.lastname: Luvison
authors.forename: Viktoria
authors.initials: V
authors.lastname: Evdokimova
authors.forename: Lindsey
authors.initials: L
authors.lastname: Kelly
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Liza C
authors.initials: LC
authors.lastname: Villaruz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D005260:Female; D005720:Gamma Rays; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008168:Lung / Q000378:metabolism / Q000528:radiation effects; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human