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Article

Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening

  • Authors:
    • Shizhang Ling
    • Eleni M. Rettig
    • Marietta Tan
    • Xiaofei Chang
    • Zhiming Wang
    • Mariana Brait
    • Justin A. Bishop
    • Elana J. Fertig
    • Michael Considine
    • Michael J. Wick
    • Patrick K. Ha
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA, Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA, Department of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD 21231, USA, South Texas Accelerated Research Therapeutics (START), Preclinical Research, 4383 Medical Drive, San Antonio, TX 78229, USA, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94158, USA
  • Pages: 225-234
    |
    Published online on: May 18, 2016
       https://doi.org/10.3892/ijo.2016.3532
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Abstract

Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2'-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; p=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the carcinogenesis of ACC.
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View References

1 

Renehan A, Gleave EN, Hancock BD, Smith P and McGurk M: Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre. Br J Surg. 83:1750–1754. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Liu J, Shao C, Tan ML, Mu D, Ferris RL and Ha PK: Molecular biology of adenoid cystic carcinoma. Head Neck. 34:1665–1677. 2012. View Article : Google Scholar

3 

Rettig EM, Tan M, Ling S, Yonescu R, Bishop JA, Fakhry C and Ha PK: MYB rearrangement and clinicopathologic characteristics in head and neck adenoid cystic carcinoma. Laryngoscope. 125:E292–E299. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Moskaluk CA: Adenoid cystic carcinoma: Clinical and molecular features. Head Neck Pathol. 7:17–22. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, Ramaswami D, Walsh LA, Eng S, Huse JT, et al: The mutational landscape of adenoid cystic carcinoma. Nat Genet. 45:791–798. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, Papaemmanuil E, Cheverton A, Bignell GR, Butler AP, et al: Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest. 123:2965–2968. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Holst VA, Marshall CE, Moskaluk CA and Frierson HF Jr: KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod Pathol. 12:956–960. 1999.PubMed/NCBI

8 

Vila L, Liu H, Al-Quran SZ, Coco DP, Dong HJ and Liu C: Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Mod Pathol. 22:1296–1302. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Tetsu O, Phuchareon J, Chou A, Cox DP, Eisele DW and Jordan RCK: Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling during tumor development in adenoid cystic carcinoma of the salivary glands. Neoplasia. 12:708–717. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Sung JY, Ahn HK, Kwon JE, Jeong H, Baek CH, Son YI, Ahn YC, Park K, Ahn MJ and Ko YH: Reappraisal of KIT mutation in adenoid cystic carcinomas of the salivary gland. J Oral Pathol Med. 41:415–423. 2012. View Article : Google Scholar

11 

Frierson HF Jr and Moskaluk CA: Mutation signature of adenoid cystic carcinoma: Evidence for transcriptional and epigenetic reprogramming. J Clin Invest. 123:2783–2785. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Ross JS, Wang K, Rand JV, Sheehan CE, Jennings TA, Al-Rohil RN, Otto GA, Curran JC, Palmer G, Downing SR, et al: Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies. Am J Surg Pathol. 38:235–238. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Mitani Y, Li J, Rao PH, Zhao YJ, Bell D, Lippman SM, Weber RS, Caulin C and El-Naggar AK: Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance. Clin Cancer Res. 16:4722–4731. 2010. View Article : Google Scholar : PubMed/NCBI

14 

West RB, Kong C, Clarke N, Gilks T, Lipsick JS, Cao H, Kwok S, Montgomery KD, Varma S and Le QT: MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation. Am J Surg Pathol. 35:92–99. 2011. View Article : Google Scholar :

15 

Brill LB II, Kanner WA, Fehr A, Andrén Y, Moskaluk CA, Löning T, Stenman G and Frierson HF Jr: Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 24:1169–1176. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Persson M, Andrén Y, Moskaluk CA, Frierson HF Jr, Cooke SL, Futreal PA, Kling T, Nelander S, Nordkvist A, Persson F, et al: Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma. Genes Chromosomes Cancer. 51:805–817. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Persson M, Andrén Y, Mark J, Horlings HM, Persson F and Stenman G: Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 106:18740–18744. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Stenman G: Fusion oncogenes in salivary gland tumors: Molecular and clinical consequences. Head Neck Pathol. 7(Suppl 1): S12–S19. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Mitani Y, Rao PH, Futreal PA, Roberts DB, Stephens PJ, Zhao YJ, Zhang L, Mitani M, Weber RS, Lippman SM, et al: Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: Association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clin Cancer Res. 17:7003–7014. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Phuchareon J, Ohta Y, Woo JM, Eisele DW and Tetsu O: Genetic profiling reveals cross-contamination and misidentification of 6 adenoid cystic carcinoma cell lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2. PLoS One. 4:e60402009. View Article : Google Scholar : PubMed/NCBI

21 

Moskaluk CA, Baras AS, Mancuso SA, Fan H, Davidson RJ, Dirks DC, Golden WL and Frierson HF Jr: Development and characterization of xenograft model systems for adenoid cystic carcinoma. Lab Invest. 91:1480–1490. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Taylor SM and Jones PA: Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 17:771–779. 1979. View Article : Google Scholar : PubMed/NCBI

23 

Jones PA and Taylor SM: Cellular differentiation, cytidine analogs and DNA methylation. Cell. 20:85–93. 1980. View Article : Google Scholar : PubMed/NCBI

24 

Cameron EE, Bachman KE, Myöhänen S, Herman JG and Baylin SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 21:103–107. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Jones PA and Taylor SM: Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells. Nucleic Acids Res. 9:2933–2947. 1981. View Article : Google Scholar : PubMed/NCBI

26 

Taylor SM and Jones PA: Mechanism of action of eukaryotic DNA methyltransferase. Use of 5-azacytosine-containing DNA. J Mol Biol. 162:679–692. 1982. View Article : Google Scholar : PubMed/NCBI

27 

Herman JG and Baylin SB: Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 349:2042–2054. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Shao C, Sun W, Tan M, Glazer CA, Bhan S, Zhong X, Fakhry C, Sharma R, Westra WH, Hoque MO, et al: Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma. Clin Cancer Res. 17:4320–4330. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Shao C, Bai W, Junn JC, Uemura M, Hennessey PT, Zaboli D, Sidransky D, Califano JA and Ha PK: Evaluation of MYB promoter methylation in salivary adenoid cystic carcinoma. Oral Oncol. 47:251–255. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Li LC and Dahiya R: MethPrimer: Designing primers for methylation PCRs. Bioinformatics. 18:1427–1431. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Kim MS, Louwagie J, Carvalho B, Terhaar Sive Droste JS, Park HL, Chae YK, Yamashita K, Liu J, Ostrow KL, Ling S, et al: Promoter DNA methylation of oncostatin m receptor-β as a novel diagnostic and therapeutic marker in colon cancer. PLoS One. 4:e65552009. View Article : Google Scholar

32 

Durr ML, Mydlarz WK, Shao C, Zahurak ML, Chuang AY, Hoque MO, Westra WH, Liegeois NJ, Califano JA, Sidransky D, et al: Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. PLoS One. 5:e108282010. View Article : Google Scholar : PubMed/NCBI

33 

Ling S, Chang X, Schultz L, Lee TK, Chaux A, Marchionni L, Netto GJ, Sidransky D and Berman DM: An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res. 71:3812–3821. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Bell D, Roberts D, Karpowicz M, Hanna EY, Weber RS and El-Naggar AK: Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma. Cancer Biol Ther. 12:569–573. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Bell A, Bell D, Weber RS and El-Naggar AK: CpG island methylation profiling in human salivary gland adenoid cystic carcinoma. Cancer. 117:2898–2909. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Santoro B, Grant SGN, Bartsch D and Kandel ER: Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels. Proc Natl Acad Sci USA. 94:14815–14820. 1997. View Article : Google Scholar

37 

Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA and Tibbs GR: Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell. 93:717–729. 1998. View Article : Google Scholar : PubMed/NCBI

38 

Ludwig A, Zong X, Jeglitsch M, Hofmann F and Biel M: A family of hyperpolarization-activated mammalian cation channels. Nature. 393:587–591. 1998. View Article : Google Scholar : PubMed/NCBI

39 

Gauss R, Seifert R and Kaupp UB: Molecular identification of a hyperpolarization-activated channel in sea urchin sperm. Nature. 393:583–587. 1998. View Article : Google Scholar : PubMed/NCBI

40 

Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F and Biel M: Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J. 18:2323–2329. 1999. View Article : Google Scholar : PubMed/NCBI

41 

Vaccari T, Moroni A, Rocchi M, Gorza L, Bianchi ME, Beltrame M and DiFrancesco D: The human gene coding for HCN2, a pacemaker channel of the heart. Biochim Biophys Acta. 1446:419–425. 1999. View Article : Google Scholar : PubMed/NCBI

42 

Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P and Kaupp UB: Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. Proc Natl Acad Sci USA. 96:9391–9396. 1999. View Article : Google Scholar : PubMed/NCBI

43 

Ishii TM, Takano M, Xie LH, Noma A and Ohmori H: Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. J Biol Chem. 274:12835–12839. 1999. View Article : Google Scholar : PubMed/NCBI

44 

Clapham DE: Not so funny anymore: Pacing channels are cloned. Neuron. 21:5–7. 1998. View Article : Google Scholar : PubMed/NCBI

45 

Hofmann F, Biel M and Kaupp UB: International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev. 57:455–462. 2005. View Article : Google Scholar : PubMed/NCBI

46 

Pape HC: Queer current and pacemaker: The hyperpolarization-activated cation current in neurons. Annu Rev Physiol. 58:299–327. 1996. View Article : Google Scholar : PubMed/NCBI

47 

Stieber J, Hofmann F and Ludwig A: Pacemaker channels and sinus node arrhythmia. Trends Cardiovasc Med. 14:23–28. 2004. View Article : Google Scholar : PubMed/NCBI

48 

DiFrancesco D: The role of the funny current in pacemaker activity. Circ Res. 106:434–446. 2010. View Article : Google Scholar : PubMed/NCBI

49 

Lang F and Stournaras C: Ion channels in cancer: Future perspectives and clinical potential. Philos Trans R Soc Lond B Biol Sci. 369:201301082014. View Article : Google Scholar : PubMed/NCBI

50 

Benarroch EE: HCN channels: Function and clinical implications. Neurology. 80:304–310. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Norberg E, Karlsson M, Korenovska O, Szydlowski S, Silberberg G, Uhlén P, Orrenius S and Zhivotovsky B: Critical role for hyperpolarization-activated cyclic nucleotide-gated channel 2 in the AIF-mediated apoptosis. EMBO J. 29:3869–3878. 2010. View Article : Google Scholar : PubMed/NCBI

52 

Michels G, Brandt MC, Zagidullin N, Khan IF, Larbig R, van Aaken S, Wippermann J and Hoppe UC: Direct evidence for calcium conductance of hyperpolarization-activated cyclic nucleotide-gated channels and human native If at physiological calcium concentrations. Cardiovasc Res. 78:466–475. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ling S, Rettig EM, Tan M, Chang X, Wang Z, Brait M, Bishop JA, Fertig EJ, Considine M, Wick MJ, Wick MJ, et al: Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening . Int J Oncol 49: 225-234, 2016.
APA
Ling, S., Rettig, E.M., Tan, M., Chang, X., Wang, Z., Brait, M. ... Ha, P.K. (2016). Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening . International Journal of Oncology, 49, 225-234. https://doi.org/10.3892/ijo.2016.3532
MLA
Ling, S., Rettig, E. M., Tan, M., Chang, X., Wang, Z., Brait, M., Bishop, J. A., Fertig, E. J., Considine, M., Wick, M. J., Ha, P. K."Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening ". International Journal of Oncology 49.1 (2016): 225-234.
Chicago
Ling, S., Rettig, E. M., Tan, M., Chang, X., Wang, Z., Brait, M., Bishop, J. A., Fertig, E. J., Considine, M., Wick, M. J., Ha, P. K."Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening ". International Journal of Oncology 49, no. 1 (2016): 225-234. https://doi.org/10.3892/ijo.2016.3532
Copy and paste a formatted citation
x
Spandidos Publications style
Ling S, Rettig EM, Tan M, Chang X, Wang Z, Brait M, Bishop JA, Fertig EJ, Considine M, Wick MJ, Wick MJ, et al: Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening . Int J Oncol 49: 225-234, 2016.
APA
Ling, S., Rettig, E.M., Tan, M., Chang, X., Wang, Z., Brait, M. ... Ha, P.K. (2016). Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening . International Journal of Oncology, 49, 225-234. https://doi.org/10.3892/ijo.2016.3532
MLA
Ling, S., Rettig, E. M., Tan, M., Chang, X., Wang, Z., Brait, M., Bishop, J. A., Fertig, E. J., Considine, M., Wick, M. J., Ha, P. K."Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening ". International Journal of Oncology 49.1 (2016): 225-234.
Chicago
Ling, S., Rettig, E. M., Tan, M., Chang, X., Wang, Z., Brait, M., Bishop, J. A., Fertig, E. J., Considine, M., Wick, M. J., Ha, P. K."Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening ". International Journal of Oncology 49, no. 1 (2016): 225-234. https://doi.org/10.3892/ijo.2016.3532
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