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.
BACKGROUND:RET rearrangement, a hallmark of radiation-induced thyroid cancer, has been reported to occur in 1% of lung adenocarcinomapatients. 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 adenocarcinomapatients with a history of therapeutic radiation for breast carcinoma or mediastinal Hodkgin lymphoma were tested for RET rearrangement by fluorescence in situ hybridization. Humanlung 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.
Authors: Yoshiyuki Suehara; Maria Arcila; Lu Wang; Adnan Hasanovic; Daphne Ang; Tatsuo Ito; Yuki Kimura; Alexander Drilon; Udayan Guha; Valerie Rusch; Mark G Kris; Maureen F Zakowski; Naiyer Rizvi; Raya Khanin; Marc Ladanyi Journal: Clin Cancer Res Date: 2012-10-10 Impact factor: 12.531
Authors: Elizabeth G Grubbs; Patrick Kwok-Shing Ng; Jacquelin Bui; Naifa L Busaidy; Ken Chen; Jeffrey E Lee; Xinyan Lu; Hengyu Lu; Funda Meric-Bernstam; Gordon B Mills; Gary Palmer; Nancy D Perrier; Kenneth L Scott; Kenna R Shaw; Steven G Waguespack; Michelle D Williams; Roman Yelensky; Gilbert J Cote Journal: J Clin Endocrinol Metab Date: 2014-12-29 Impact factor: 5.958
Authors: Oliver Gautschi; Julie Milia; Thomas Filleron; Juergen Wolf; David P Carbone; Dwight Owen; Ross Camidge; Vignhesh Narayanan; Robert C Doebele; Benjamin Besse; Jordi Remon-Masip; Pasi A Janne; Mark M Awad; Nir Peled; Chul-Cho Byoung; Daniel D Karp; Michael Van Den Heuvel; Heather A Wakelee; Joel W Neal; Tony S K Mok; James C H Yang; Sai-Hong Ignatius Ou; Georg Pall; Patrizia Froesch; Gérard Zalcman; David R Gandara; Jonathan W Riess; Vamsidhar Velcheti; Kristin Zeidler; Joachim Diebold; Martin Früh; Sebastian Michels; Isabelle Monnet; Sanjay Popat; Rafael Rosell; Niki Karachaliou; Sacha I Rothschild; Jin-Yuan Shih; Arne Warth; Thomas Muley; Florian Cabillic; Julien Mazières; Alexander Drilon Journal: J Clin Oncol Date: 2017-03-13 Impact factor: 44.544