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In a screen for thoracic malignancy-associated markers, thyroid stimulatinghormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterizedlung cancer marker NKX2-1. We screened for mutations in all coding regions ofthe TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normallung samples. We found one patient with a somatic mutation at codon 458 (exon10), which is located at the transmembrane domain where most TSHR mutations havebeen found in thyroid-related diseases. This patient had lung adenocarcinoma withBAC (bronchioloalveolar carcinoma) features in the setting of a prior medicalhistory significant for carotid stenosis and severe chronic obstructive pulmonarydisease (COPD). In order to characterize the genetic features of TSHR in lungcancer, we checked for TSHR expression and copy number in the 96 lung cancer tissues.TSHR protein expression was generally overexpressed in multiple thoracic malignancies(adenocarcinoma, squamous cell carcinoma and malignant pleural mesothelioma) byimmunohistochemistry. Our data suggest that aberrant TSHR function may contributeto lung cancer development or a subgroup of lung cancer with specific clinicalphenotypes.

oncology reports

A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease