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Novel Developments in the Molecular Genetic Basis of Oral Squamous Cell Carcinoma (OSCC)

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Development of Oral Cancer

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Abstract

According to the Oral Cancer Foundation, “The death rate for oral cancer is higher than that of cancers which we hear about routinely.” In America, the number of diagnosed cases is approximately 54,000 individuals. WHO best estimate is that worldwide the number is well over 450,000 of new cases being found each year. Oral cancer is considered extremely dangerous for two reasons: (1) typically early stages go unnoticed by the patient because of no pain signs or recognizable symptoms and (2) the high risk of producing second, primary tumors. There are several types of oral cancers, but around 90% are squamous cell carcinomas (OSCC). The condition is very taxing to any healthcare system. For instance, approximately $3.2 billion is spent in the USA alone. Therefore, full comprehension of the oral cancer disease is overriding in order to design effective modalities. This can be accomplished only by advancing our understanding of oral cancer at the molecular level. In this chapter, we will focus on the most important and common molecular genetic alterations at the genomic, epigenetic, and transcriptomic levels and study changes in tumor suppressor genes (TSGs), oncogenes, gene expression, epigenetic and genomic instability, mitochondrial DNA (mtDNA) mutations, noncoding RNA, and loss of heterozygosity (LOH) in OSCC. It is not the intent of this chapter to provide detailed information or review the literature. Rather, the effort will be directed to highlight either latest advancements, our collective understanding, or salient features of OSCC. We will conclude the chapter with the viewpoint of the importance of further research (disease models, targeted therapy, and treatment), value of biomarkers and early detection, and patient education/public awareness.

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References

  1. Nebert DW. Transcription factors and cancer: an overview. Toxicology. 2002;181–182:131–41.

    Article  PubMed  Google Scholar 

  2. Kinzler KW, Vogelstein B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature. 1997;386(6627):761–3.

    Article  CAS  PubMed  Google Scholar 

  3. Michor F, Iwasa Y, Nowak MA. Dynamics of cancer progression. Nat Rev Cancer. 2004;4(3):197–205.

    Article  CAS  PubMed  Google Scholar 

  4. Ram H, et al. Oral cancer: risk factors and molecular pathogenesis. J Maxillofac Oral Surg. 2011;10(2):132–7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jurel SK, et al. Genes and oral cancer. Indian J Hum Genet. 2014;20(1):4–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nakaya K, et al. Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array. Oncogene. 2007;26(36):5300–8.

    Article  CAS  PubMed  Google Scholar 

  7. Morris LG, et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat Genet. 2013;45(3):253–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Riaz N, et al. Unraveling the molecular genetics of head and neck cancer through genome-wide approaches. Genes Dis. 2014;1(1):75–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kim KT, Kim BS, Kim JH. Association between FAT1 mutation and overall survival in patients with human papillomavirus-negative head and neck squamous cell carcinoma. Head Neck. 2016;38(Suppl 1):E2021–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Glazer CA, et al. Applying the molecular biology and epigenetics of head and neck cancer in everyday clinical practice. Oral Oncol. 2009;45(4–5):440–6.

    Article  CAS  PubMed  Google Scholar 

  11. Sakai E, et al. The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous-cell carcinoma. Int J Cancer. 1992;52(6):867–72.

    Article  CAS  PubMed  Google Scholar 

  12. Nakamura E, et al. Frequent silencing of a putative tumor suppressor gene melatonin receptor 1 a (MTNR1A) in oral squamous-cell carcinoma. Cancer Sci. 2008;99(7):1390–400.

    Article  CAS  PubMed  Google Scholar 

  13. Kurasawa Y, et al. PTEN expression and methylation status in oral squamous cell carcinoma. Oncol Rep. 2008;19(6):1429–34.

    CAS  PubMed  Google Scholar 

  14. Arya V, Singh S, Daniel MJ. Clinicopathological correlation of bcl-2 oncoprotein expression in oral precancer and cancer. J Oral Biol Craniofac Res. 2016;6(1):18–23.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Murugan AK, Munirajan AK, Tsuchida N. Ras oncogenes in oral cancer: the past 20 years. Oral Oncol. 2012;48(5):383–92.

    Article  CAS  PubMed  Google Scholar 

  16. Shah NG, et al. Prognostic significance of molecular markers in oral squamous cell carcinoma: a multivariate analysis. Head Neck. 2009;31(12):1544–56.

    Article  PubMed  Google Scholar 

  17. Pérez-Sayáns M, et al. What real influence does the proto-oncogene c-myc have in OSCC behavior? Oral Oncol. 2011;47(8):688–92.

    Article  PubMed  Google Scholar 

  18. Sartini D, et al. Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis. Oral Dis. 2015;21(4):462–9.

    Article  CAS  PubMed  Google Scholar 

  19. Maeda T, et al. Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature. 2005;433(7023):278–85.

    Article  CAS  PubMed  Google Scholar 

  20. Peiqi L, et al. Expression of SRSF3 is correlated with carcinogenesis and progression of oral squamous cell carcinoma. Int J Med Sci. 2016;13(7):533–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xu S, et al. DJ-1 is upregulated in oral squamous cell carcinoma and promotes oral cancer cell proliferation and invasion. J Cancer. 2016;7(8):1020–8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kozaki K-I, et al. PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci. 2006;97(12):1351–8.

    Article  CAS  PubMed  Google Scholar 

  23. Zanaruddin SN, et al. Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin. PLoS One. 2013;8(11):e80229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sumino J, et al. Gene expression changes in initiation and progression of oral squamous cell carcinomas revealed by laser microdissection and oligonucleotide microarray analysis. Int J Cancer. 2013;132(3):540–8.

    Article  CAS  PubMed  Google Scholar 

  25. Chakraborty S, et al. Gene expression profiling of oral squamous cell carcinoma by differential display rt-PCR and identification of tumor biomarkers. Indian J Surg Oncol. 2010;1(4):284–93.

    Article  PubMed  Google Scholar 

  26. Lohavanichbutr P, et al. Gene expression in uninvolved oral mucosa of OSCC patients facilitates identification of markers predictive of OSCC outcomes. PLoS One. 2012;7(9):e46575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Oliveira-Costa JP, et al. Gene expression patterns through oral squamous cell carcinoma development. FASEB J. 2013;27(Suppl 1):lb473.

    Google Scholar 

  28. Chen C, et al. Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiol Biomark Prev. 2008;17(8):2152–62.

    Article  CAS  Google Scholar 

  29. Osathanon T, Nowwarote N, Pavasant P. Expression and influence of Notch signaling in oral squamous cell carcinoma. J Oral Sci. 2016;58(2):283–94.

    Article  PubMed  Google Scholar 

  30. Paterson IC, et al. Decreased expression of TGF-beta cell surface receptors during progression of human oral squamous cell carcinoma. J Pathol. 2001;193(4):458–67.

    Article  CAS  PubMed  Google Scholar 

  31. Rich AM, et al. Toll-like receptors and cancer, particularly oral squamous cell carcinoma. Front Immunol. 2014;5:464.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lee BK, et al. A high concentration of MMP-2/gelatinase a and MMP-9/gelatinase B reduce NK cell-mediated cytotoxicity against an oral squamous cell carcinoma cell line. In Vivo. 2008;22(5):593–7.

    CAS  PubMed  Google Scholar 

  33. Silva SD, et al. ErbB2 and fatty acid synthase (FAS) expression in 102 squamous cell carcinomas of the tongue: correlation with clinical outcomes. Oral Oncol. 2008;44(5):484–90.

    Article  CAS  PubMed  Google Scholar 

  34. Mahendra A, et al. Epidermal growth factor receptor protein: a biological marker for oral precancer and cancer. J Dent Surg. 2014;2014:7.

    Article  Google Scholar 

  35. Gasche JA, Goel A. Epigenetic mechanisms in oral carcinogenesis. Future Oncol. 2012;8(11):1407–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ha PK, Califano JA. Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma. Lancet Oncol. 2006;7(1):77–82.

    Article  CAS  PubMed  Google Scholar 

  37. Jawert F, et al. Loss of 5-hydroxymethylcytosine and TET2 in oral squamous cell carcinoma. Anticancer Res. 2013;33(10):4325–8.

    PubMed  Google Scholar 

  38. Koike K, et al. High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer. Int J Oncol. 2013;42(1):141–50.

    CAS  PubMed  Google Scholar 

  39. Mascolo M, et al. Epigenetic dysregulation in oral cancer. Int J Mol Sci. 2012;13(2):2331–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Vincent-Chong VK, et al. Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9. PLoS One. 2013;8(2):e54705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Castagnola P, et al. Genomic DNA copy number aberrations, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. PLoS One. 2015;10(11):e0142294.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sun Y, et al. Screening of the gene mutation in D-loop region of mitochondrial DNA in oral squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi. 2013;48(5):285–7.

    CAS  PubMed  Google Scholar 

  43. Yuan RT, et al. Gene mutations in the D-loop region of mitochondrial DNA in oral squamous cell carcinoma. Mol Med Rep. 2015;11(6):4496–500.

    CAS  PubMed  Google Scholar 

  44. Mondal R, Ghosh SK. Accumulation of mutations over the complete mitochondrial genome in tobacco-related oral cancer from northeast India. Mitochondrial DNA. 2013;24(4):432–9.

    Article  CAS  PubMed  Google Scholar 

  45. Kloss-Brandstatter A, et al. Validation of next-generation sequencing of entire mitochondrial genomes and the diversity of mitochondrial DNA mutations in oral squamous cell carcinoma. PLoS One. 2015;10(8):e0135643.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Uzawa K, et al. Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma. Oncotarget. 2012;3(7):670–7.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sainger RN, et al. Clinical significance of telomere length and associated proteins in oral cancer. Biomark Insights. 2007;2:9–19.

    PubMed  PubMed Central  Google Scholar 

  48. Chen HH, et al. Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan. Oral Oncol. 2007;43(2):122–9.

    Article  CAS  PubMed  Google Scholar 

  49. Ashazila MJ, et al. Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population. Oral Oncol. 2011;47(5):358–64.

    Article  CAS  PubMed  Google Scholar 

  50. Lin SC, et al. Frequent microsatellite alterations of chromosome locus 4q13.1 in oral squamous cell carcinomas. J Oral Pathol Med. 2005;34(4):209–13.

    Article  CAS  PubMed  Google Scholar 

  51. Mahale A, Saranath D. Microsatellite alterations on chromosome 9 in chewing tobacco-induced oral squamous cell carcinomas from India. Oral Oncol. 2000;36(2):199–206.

    Article  CAS  PubMed  Google Scholar 

  52. Shin K.-H, et al. Prevalence of microsatellite instability, inactivation of mismatch repair genes, p53 mutation, and human papillomavirus infection in Korean oral cancer patients. Int J Oncol. 2002;21(2):297–302(6).

    Google Scholar 

  53. Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tang G, et al. Construction of short tandem target mimic (STTM) to block the functions of plant and animal microRNAs. Methods. 2012;58(2):118–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11(4):441–50.

    Article  CAS  PubMed  Google Scholar 

  56. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5.

    Article  CAS  PubMed  Google Scholar 

  57. Hebert C, et al. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer. 2007;6:5.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Wong TS, et al. Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling. Int J Cancer. 2008;123(2):251–7.

    Article  CAS  PubMed  Google Scholar 

  59. Yu T, et al. The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthracene-induced oral carcinogenesis in Syrian hamster. J Exp Clin Cancer Res. 2009;28:64.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Peng SC, et al. MicroRNAs MiR-218, MiR-125b, and let-7g predict prognosis in patients with oral cavity squamous cell carcinoma. PLoS One. 2014;9(7):e102403.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sun Q, et al. Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting podoplanin. Int J Biochem Cell Biol. 2013;45(3):513–20.

    Article  CAS  PubMed  Google Scholar 

  62. Yu T, et al. MicroRNA-9 inhibits the proliferation of oral squamous cell carcinoma cells by suppressing expression of CXCR4 via the wnt/beta-catenin signaling pathway. Oncogene. 2014;33(42):5017–27.

    Article  CAS  PubMed  Google Scholar 

  63. Wong TS, et al. Mature miR-184 and squamous cell carcinoma of the tongue. ScientificWorldJournal. 2009;9:130–2.

    Article  PubMed  Google Scholar 

  64. Wong TS, et al. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res. 2008;14(9):2588–92.

    Article  CAS  PubMed  Google Scholar 

  65. Ramdas L, et al. miRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 2009;31(5):642–54.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Jung HM, et al. Keratinization-associated miR-7 and miR-21 regulate tumor suppressor reversion-inducing cysteine-rich protein with kazal motifs (RECK) in oral cancer. J Biol Chem. 2012;287(35):29261–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gee HE, et al. Hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer. 2010;116(9):2148–58.

    PubMed  Google Scholar 

  68. Shiiba M, et al. MicroRNA-125b regulates proliferation and radioresistance of oral squamous cell carcinoma. Br J Cancer. 2013;108(9):1817–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sasahira T, et al. Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer. Br J Cancer. 2012;107(4):700–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chi H. miR-194 regulated AGK and inhibited cell proliferation of oral squamous cell carcinoma by reducing PI3K-akt-FoxO3a signaling. Biomed Pharmacother. 2015;71:53–7.

    Article  CAS  PubMed  Google Scholar 

  71. Kozaki K, et al. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68(7):2094–105.

    Article  CAS  PubMed  Google Scholar 

  72. Deng L, Liu H. MicroRNA-506 suppresses growth and metastasis of oral squamous cell carcinoma via targeting GATA6. Int J Clin Exp Med. 2015;8(2):1862–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Huang WC, et al. miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer Res. 2014;74(3):751–64.

    Article  CAS  PubMed  Google Scholar 

  74. Chang CC, et al. MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma. Oral Oncol. 2013;49(9):923–31.

    Article  CAS  PubMed  Google Scholar 

  75. Zheng M, et al. Snail and slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma. Oncotarget. 2015;6(9):6797–810.

    Article  PubMed  Google Scholar 

  76. Liu CJ, et al. miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene. Int J Cancer. 2014;134(4):811–21.

    Article  CAS  PubMed  Google Scholar 

  77. Xu Q, et al. Downregulation of miR-153 contributes to epithelial-mesenchymal transition and tumor metastasis in human epithelial cancer. Carcinogenesis. 2013;34(3):539–49.

    Article  CAS  PubMed  Google Scholar 

  78. Yang CC, et al. miR-181 as a putative biomarker for lymph-node metastasis of oral squamous cell carcinoma. J Oral Pathol Med. 2011;40(5):397–404.

    Article  CAS  PubMed  Google Scholar 

  79. Pan YF, et al. Role of long non-coding RNAs in gene regulation and oncogenesis. Chin Med J. 2011;124(15):2378–83.

    CAS  PubMed  Google Scholar 

  80. Denaro N, et al. Non coding RNAs in head and neck squamous cell carcinoma (HNSCC): a clinical perspective. Anticancer Res. 2014;34(12):6887–96.

    CAS  PubMed  Google Scholar 

  81. Gibb EA, et al. Long non-coding RNAs are expressed in oral mucosa and altered in oral premalignant lesions. Oral Oncol. 2011;47(11):1055–61.

    Article  CAS  PubMed  Google Scholar 

  82. Yang YT, et al. Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/beta-catenin signaling pathway. Cancer Sci. 2016;107(11):1581–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Fang Z, et al. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(1):89–95.

    Article  PubMed  Google Scholar 

  84. Wu Y, et al. Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol. 2015;46(6):2586–94.

    CAS  PubMed  Google Scholar 

  85. Gao W, Chan JY, Wong TS. Long non-coding RNA deregulation in tongue squamous cell carcinoma. Biomed Res Int. 2014;2014:405860.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Qatar Medical Genetics Center (QMGC), Interim Translational Research Institute (iTRI), HMC, P.O. Box 3050, Doha, Qatar

    Nader I Al-Dewik

  2. Faculty of Health and Social Care Sciences, Kingston University, St George’s University of London, London, UK

    Nader I Al-Dewik

  3. Biotechnology Development Department, Qatar Biomedical Research Institute (QBRI), Hamad bin Khalifa University (HBKU), P.O. Box 34110, Doha, Qatar

    M. Walid Qoronfleh

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  1. Nader I Al-Dewik
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  2. M. Walid Qoronfleh
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Correspondence to Nader I Al-Dewik .

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  1. Department of Basic Medical Science, Qatar University/College of Medicine, Doha, Qatar

    Ala-Eddin Al Moustafa

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Al-Dewik, N.I., Qoronfleh, M.W. (2017). Novel Developments in the Molecular Genetic Basis of Oral Squamous Cell Carcinoma (OSCC). In: Al Moustafa, AE. (eds) Development of Oral Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48054-1_2

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