title: Low incidence of IL6ST (gp130) mutations in exon 6 in lung cancer of a Chinese cohort.
abstract: Lung cancer is an inflammation-associated epithelial carcinoma. A highly active interleukin 6 (IL-6)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway has been identified in a subset of primary lung cancer and closely correlated with tumor progression and poor prognosis. In a previous study, the frequent occurrence of somatic gain-of-function mutations was observed in the gp130-encoding IL6ST gene in exon 6 in 60% of inflammatory hepatocellular adenomas. Prompted by this finding, we assessed 110 Chinese lung carcinomas using PCR and direct DNA sequencing but found no somatic mutation of IL6ST in exon 6. However, one new potential germline missense mutation c.599C>G was identified in one adenocarcinoma that harbors wild-type epidermal growth factor receptor and KRAS. Protein modeling analysis showed that this mutation might not affect the gp130 protein conformation. Moreover, activated STAT3 was observed in most of the lung tumor tissues at a higher level than that in matched normal lung tissues. In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Luguo
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Life Science, Jilin University, Changchun, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Sui
authors.affiliation: Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Xianling
authors.initials: X
authors.lastname: Cong
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Kejuan
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Pathology, The First Hospital, Jilin University, Changchun, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Ma
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Fan
authors.affiliation: College of Life Science, Jilin University, Changchun, China.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.affiliation: Cancer Center, The First Hospital, Jilin University, Changchun, China. Electronic address: makw@jlu.edu.cn.
authors.forename: Kewei
authors.initials: K
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D055752:Small Cell Lung Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C494199:IL6ST protein, human; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130
keywords: Lung cancer; STAT3; exon 6; gp130; mutation