title: Identification of guanine nucleotide-binding protein γ-7 as an epigenetically silenced gene in head and neck cancer by gene expression profiling.
abstract: Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. Aberrant hypermethylation in the promoter region of some known or putative tumor suppressor genes occurs frequently during the development of various types of cancer including head and neck squamous cell carcinoma (HNSCC). In this study we used an expanded mRNA expression profiling approach followed by microarray expression analysis to identify epigenetically inactivated genes in HNSCC. Two HNSCC cell lines were treated with 5-aza-2'-deoxycytidine followed by microarray analysis to identify epigenetically silenced genes in HNSCC. We found 1,960, 614 and 427 genes were upregulated in the HNSCC cell lines JHU-012, JHU-011 and the combination of both cell lines, respectively. HNSCC tumor and normal mucosal samples were used for gene profiling by a 47K mRNA gene expression array and we found 7,140 genes were downregulated in HNSCC tumors compared to normal mucosa, as determined by microarray analysis, and were integrated with cell line data. Integrative analysis defined 126 candidate genes, of which only seven genes showed differential methylation in tumors and no methylation in normal mucosa after bisulfite sequencing. Following validation by QMSP, one gene, guanine nucleotide-binding protein γ-7 (GNG7), was confirmed to be highly methylated in tumors and unmethylated in normal mucosal and salivary rinse samples demonstrating cancer-specific methylation in HNSCC tissues. TXNIP and TUSC2 were partially methylated in tumors and normal salivary rinses but unmethylated in normal mucosa. We concluded that GNG7 is a highly specific promoter methylated gene associated with HNSCC. In addition, TXNIP and TUSC2 are also potential biomarkers for HNSCC.
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA. demokan@istanbul.edu.tr
authors: Semra
authors: S
authors: Demokan
authors: Alice Y
authors: AY
authors: Chuang
authors: Xiaofei
authors: X
authors: Chang
authors: Tanbir
authors: T
authors: Khan
authors: Ian M
authors: IM
authors: Smith
authors: Kavita M
authors: KM
authors: Pattani
authors: Santanu
authors: S
authors: Dasgupta
authors: Shahnaz
authors: S
authors: Begum
authors: Zubair
authors: Z
authors: Khan
authors: Nanette J
authors: NJ
authors: Liegeois
authors: William H
authors: WH
authors: Westra
authors: David
authors: D
authors: Sidransky
authors: Wayne
authors: W
authors: Koch
authors: Joseph A
authors: JA
authors: Califano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C527544:GNG7 protein, human; D044388:GTP-Binding Protein gamma Subunits; C499993:TUSC2 protein, human; C486715:TXNIP protein, human; D025521:Tumor Suppressor Proteins
references: Mol Cancer. 2009 Oct 24;8:91
references: 19852844
references: Clin Cancer Res. 2008 Jan 1;14(1):41-7
references: 18172250
references: Bioinformatics. 2002 Nov;18(11):1427-31
references: 12424112
references: J Biol Chem. 1995 Sep 15;270(37):21765-71
references: 7665596
references: Cell. 1990 Jun 1;61(5):759-67
references: 2188735
references: Adv Cancer Res. 1998;72:141-96
references: 9338076
references: Oncogene. 2001 Sep 27;20(43):6258-62
references: 11593436
references: Biochem Biophys Res Commun. 1998 May 8;246(1):205-9
references: 9600093
references: Nucleic Acids Res. 2000 Apr 15;28(8):E32
references: 10734209
references: J Neurochem. 1996 May;66(5):2213-6
references: 8780057
references: Clin Cancer Res. 2008 Jan 1;14(1):97-107
references: 18172258
references: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3900-5
references: 20133584
references: J Biol Chem. 1999 Jul 30;274(31):21645-50
references: 10419473
references: Cancer Cell. 2002 Dec;2(6):485-95
references: 12498717
references: Br J Cancer. 2008 Jan 29;98(2):410-7
references: 18219292
references: N Engl J Med. 2003 Nov 20;349(21):2042-54
references: 14627790
references: J Cell Biochem Suppl. 2000;Suppl 35:78-83
references: 11389535
references: Br J Haematol. 2008 Sep;142(6):916-24
references: 18671701
references: Nan Fang Yi Ke Da Xue Xue Bao. 2009 Apr;29(4):645-7
references: 19403385
references: Clin Chem. 2002 Aug;48(8):1178-85
references: 12142370
references: Hematol Oncol Stem Cell Ther. 2010;3(2):66-70
references: 20543539
references: J Natl Cancer Inst. 2001 Nov 21;93(22):1747-52
references: 11717336
references: PLoS One. 2011;6(5):e20584
references: 21637785
references: J Biol Chem. 1988 Oct 25;263(30):15506-12
references: 3170595
references: Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6189-93
references: 15448006
references: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references: 11309499
references: Cancer Res. 2004 May 1;64(9):2969-76
references: 15126327
references: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references: 16514137
references: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references: 11134512
references: Cancer Res. 2004 Sep 1;64(17):5982-7
references: 15342377
references: Oncogene. 2003 Jun 26;22(26):4035-46
references: 12821938
references: Ann N Y Acad Sci. 2003 Mar;983:120-30
references: 12724217
references: Cancer Res. 2000 Nov 1;60(21):6116-33
references: 11085536