title: Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer.
abstract: BACKGROUND
  Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA).
  
  
  RESULTS
  Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression.
  
  
  CONCLUSIONS
  These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, United States of America, 94143.
authors.forename: Noah D
authors.initials: ND
authors.lastname: Peyser
authors.affiliation: Department of Otolaryngology, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States of America, 15213.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Pendleton
authors.affiliation: Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States of America, 15213.
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.affiliation: Department of Pharmacology and Pharmacy, School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Vivian W Y
authors.initials: VW
authors.lastname: Lui
authors.affiliation: Department of Medicine, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Johnson
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, United States of America, 94143.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D053181:Caspase 8