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

Kim,James  Wan Soo; Lee,Sharon; Lui,Natalie; Choi,Helen; Mulvihill,Michael; Fang,Li  Tai; Kang,Hio  Chung; Kwon,Yong-Won; Jablons,David; Kim,Il-Jin

doi:10.3892/or.2012.1938

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

Authors:
- James Wan Soo Kim
- Sharon Lee
- Natalie Lui
- Helen Choi
- Michael Mulvihill
- Li Tai Fang
- Hio Chung Kang
- Yong-Won Kwon
- David Jablons
- Il-Jin Kim
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Affiliations: Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA, Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA, Life Sciences Division, Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA, USA
Published online on: July 26, 2012 https://doi.org/10.3892/or.2012.1938
Pages: 1225-1230

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Abstract

In a screen for thoracic malignancy-associated markers, thyroid stimulating hormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterized lung cancer marker NKX2-1. We screened for mutations in all coding regions of the TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normal lung samples. We found one patient with a somatic mutation at codon 458 (exon 10), which is located at the transmembrane domain where most TSHR mutations have been found in thyroid-related diseases. This patient had lung adenocarcinoma with BAC (bronchioloalveolar carcinoma) features in the setting of a prior medical history significant for carotid stenosis and severe chronic obstructive pulmonary disease (COPD). In order to characterize the genetic features of TSHR in lung cancer, 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) by immunohistochemistry. Our data suggest that aberrant TSHR function may contribute to lung cancer development or a subgroup of lung cancer with specific clinical phenotypes.

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