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Tumor Biology

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19.12.2015 | Original Article

PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population

verfasst von: P. S. Sushma, Kaiser Jamil, P. Uday Kumar, U. Satyanarayana, M. Ramakrishna, B. Triveni

Erschienen in: Tumor Biology | Ausgabe 6/2016

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Abstract

Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.

Ogbureke KU, Bingham C. Overview of oral cancer. In: Ogbureke KU, editor. Oral cancer. Croatia: Intech; 2012. p. 3–20.CrossRef

Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16.CrossRefPubMed

Kyrgidis A, Tzellos TG, Triaridis S. Melanoma: stem cells, sun exposure and hallmarks for carcinogenesis, molecular concepts and future clinical implications. J Carcinog. 2010;9:3.CrossRefPubMedPubMedCentral

Esteller M. Cancer epigenetics: DNA methylation and chromatin alterations in human cancer. AdvExp Med Biol. 2003;532:39–49.CrossRef

Myers MP, Stolarov J, Eng C, Li J, Wang SI, Wigler MH, et al. PTEN, the tumor suppressor from human chromosome 10q23, is a dual specificity phosphatase. Proc Natl Acad Sci U S A. 1997;94:9052–7.CrossRefPubMedPubMedCentral

Chang SH. Loss of PTEN expression in breast cancers. Korean J Pathol. 2005;39:236–41.

Tsuda H, Hashiguchi Y, Nishimura S, Kawamura N, Inoue T, Yamamoto K. Relationship between HPV typing and abnormality of G1 cell cycle regulators in cervical neoplasm. Gynecol Oncol. 2003;91(3):476–85.CrossRefPubMed

Ah I, Rashid M, Sameer G, Jamsheed. Inactivation of P16 (INK4a) gene by promoter hypermethylation is associated with disease progression in chronic myelogenous leukaemia. Carcinog Mutagen. 2013;4:2.

Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96.PubMed

10.

Kawaguchi K, Oda Y, Saito T, Yamamoto H, Takahira T, et al. DNA hypermethylation status of multiple genes in soft tissue sarcomas. Mod Pathol. 2006;19:106–14.CrossRefPubMed

11.

Kawaguchi K, Oda Y, Saito T, Takahira T, Yamamoto H, et al. Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcoma. Hum Pathol. 2005;36:357–63.CrossRefPubMed

12.

Andjelkovic T, Bankovic J, Milosevic Z, Stojsic J, Milinkovic V, Pesic M, et al. Concurrent alteration of p16 and PTEN tumor suppressor genes could be considered as potential molecular marker for specific subgroups of NSCLC patients. Cancer Biomark. 2012;10:277–86.

13.

Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15:356–62.CrossRefPubMed

14.

Ma X, Ziel-van der Made AC, Autar B, et al. Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res. 2005;65:5730–9.CrossRefPubMed

15.

Song B, Ai J, Kong X, Liu D, Li J. Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in gastric cancer. Pak J Med Sci. 2013;29(6):1338–43.PubMedPubMedCentral

16.

Belinsky SA, Klinge DM, Dekker JD, Smith MW, Bocklage TJ, Gilliland FD, et al. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res. 2005;11(18):6505–11.CrossRefPubMed

17.

Hsu LS, Lee HC, Chau GY, Yin PH, Chi CW, Lui WY. Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncol Rep. 2006;15(2):507–11.PubMed

18.

Mino A, Onoda N, Yashiro M, Aya M, Fujiwara I, Kubo N, et al. Frequent p16 CpG island hypermethylation in primary remnant gastric cancer suggesting an independent carcinogenic pathway. Oncol Rep. 2006;15(3):615–20.PubMed

19.

Askari M, Sobti RC, Nikbakht M, Sharma SC. Promoter hypermethylation of tumour suppressor genes (p14/ARF and p16/INK4a): case–control study in North Indian population. Mol Biol Rep. 2013;40(8):4921–8.CrossRefPubMed

20.

Alyasiri NS et al. Aberrant promoter methylation of PTEN gene among Indian patients with oral squamous cell carcinoma. Int J Biol Markers. 2013;28(3):298–302.CrossRefPubMed

21.

Goel A et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 2004;64:3014.CrossRefPubMed

22.

Shaw RJ, Cantley LC. Ras, PI (3)K and mTORsignalling controls tumour cell growth. Nature. 2006;441:424–30.CrossRefPubMed

23.

Janzen V, Scadden DT. Stem cells: good, bad and reformable. Nature. 2006;441:418–9.CrossRefPubMed

24.

Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem. 1999;274:20693–703.CrossRefPubMed

25.

Nagalakshmi K, Jamil K, Pingali UR, Addala L, Naidu M. Association of PIK3CA gene mutations with head and neck squamous cell carcinomas. Neoplasma. 2015;62(1):72–80.CrossRef

26.

Nagalakshmi K, Jamil K, Pingali U, Vishnuvardhan Reddy M, Attili SSV. Epidermal growth factor receptor (EGFR) mutations as biomarker for head and neck squamous cell carcinomas (HNSCC). Biomarkers. 2014, Early Online: 1–9, 2014 Informa UK Ltd. doi:10.3109/1354750X.2014.895852

27.

Nagalakshmi K, Jamil K, Rani PU. Association of EGFR gene polymorphism in head and neck cancer patients with tobacco and alcohol consuming habits. Biol Med. 2013;5:69–77.

28.

Subhani S, Jayaraman A, Jamil K. Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer. Biomed Pharmacother. 2015;71. doi:10.1016/j.biopha.2015.02.009 2.239 Impact Factor.

29.

Jamil K. Clinical implications of MTHFR gene polymorphism in various diseases. OMICS. 2014;6, e107. doi:10.4172/0974-8369.1000e107.

30.

Sabitha K, Reddy MVV, Jamil K. Mutations in XRCC1 gene altering the genetic risks of head and neck cancer patients. Int J Cancer Res. 2009;5(2):58–68.CrossRef

31.

Sabitha K, Reddy MVV, Jamil K. GST genotypes in head and neck cancer patients and its clinical implications. Afr J Biotechnol. 2008;7(21):3853–9. Available online at, http://www.ajol.info/index.php/ajb/article/view/59456/47747 .

32.

Kotra S, Madala KK, Jamil K. Homology models of the mutated EGFR and their response towards quinazolin analogues. J Mol Graph Model. 2008;27:244–54.CrossRefPubMed

33.

Jamil K. Biomarkers in oncological research. Editorial. J Cancer Sci Ther. 2015;7(9):134. doi:10.4172/1948-5956.1000e134.

34.

Liu HW, Hu BQ, Cao CF. The p16 methylation in oral leukoplakia and oral squamous cell carcinoma. Zhonghua Kou Qiang Yi XueZaZhi. 2005;40:94–7.

35.

Shi H et al. Association between P16INK4a promoter methylation and HNSCC: a meta-analysis of 21 published studies. PLoS One. 2014. doi:10.1371/journal.pone.0122302.

36.

Okami K, Sakai A, Onuki J, Hamano T, Iida M, Takahashi M. Promoter hypermethylation of tumor-associated genes in head and neck cancer. Nihon JibiinkokaGakkaiKaiho. 2005;108:207–13.CrossRef

37.

Huang MJ, Yeh KT, Shih HC, Wang YF, Lin TH, Chang JY, et al. The correlation between CpG methylation and protein expression of P16 in oral squamous cell carcinomas. Int J Mol Med. 2002;10:551–4.PubMed

38.

Ai L, Stephenson KK, Ling W, Zuo C, Mukunyadzi P, Suen JY, et al. The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases. Mod Pathol. 2003;16:944–50.CrossRefPubMed

Titel: PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population
verfasst von: P. S. Sushma
Kaiser Jamil
P. Uday Kumar
U. Satyanarayana
M. Ramakrishna
B. Triveni
Publikationsdatum: 19.12.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 6/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4648-8

Springer Medizin

PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population

Abstract

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