A Functional Polymorphism in CSF1R Gene Is a Novel Susceptibility Marker for Lung Cancer among Never-Smoking Females Hyo-Gyoung Kang, PhD, Shin Yup Lee,

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A Functional Polymorphism in CSF1R Gene Is a Novel Susceptibility Marker for Lung Cancer among Never-Smoking Females Hyo-Gyoung Kang, PhD, Shin Yup Lee, MD, PhD, Hyo-Sung Jeon, PhD, Yi Young Choi, PhD, Soyoun Kim, PhD, Won Kee Lee, PhD, Hyun Chul Lee, MSc, Jin Eun Choi, PhD, Eun Young Bae, MSc, Seung Soo Yoo, MD, PhD, Jaehee Lee, MD, Seung Ick Cha, MD, Chang Ho Kim, MD, Myung Hoon Lee, PhD, Young Tae Kim, MD, Jin Hee Kim, PhD, Yun-Chul Hong, MD, Yeul Hong Kim, MD, Jae Yong Park, MD, PhD Journal of Thoracic Oncology Volume 9, Issue 11, Pages 1647-1655 (November 2014) DOI: 10.1097/JTO.0000000000000310 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Homology-based model for CSF1R wild type (H362) and variant type (R362). A, The homology models of CSF1R dimer (colored with yellow and green) were built using the SWISS-PRO and MODELLER program (v9.2) using the complex structure of ectodomain of KIT (purple) and CSF1 (blue and light blue) (2e9w); (B) single nucleotide polymorphism (SNP) residue histidine is highlighted in yellow; (C) the surface electrostatic potential of wild type and variant type CSF1R was calculated using DelPhi calculation; (D) the surface electrostatic potential of CSF1 was viewed. All figures are displayed using Pymol (http://www.pymol. org). Journal of Thoracic Oncology 2014 9, 1647-1655DOI: (10.1097/JTO.0000000000000310) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 In vitro functional analyses of CSF1R variant type (R362). Western blot of lysates from wild type (H362) or variant type (R362) transfected 293T cells treated with M-CSF (20 ng/ml) for 20 minutes. Lysates from untreated CSF1R-transfected cells were included as a control. Actin was used as internal control. Flag antibody detected the wild type (H362) and variant type (R362). Experiments were repeated three times with similar outcome. All blots are representative of at least four to six blots from three independent experiments. M-CSF, macrophage colony-stimulating factor. Journal of Thoracic Oncology 2014 9, 1647-1655DOI: (10.1097/JTO.0000000000000310) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions