TY  - JOUR
AU  - Nikolić, Nađa
AU  - Čarkić, Jelena
AU  - Ilić Dimitrijević, Ivana
AU  - Eljabo, Najib
AU  - Radunović, Milena
AU  - Aničić, Boban
AU  - Tanić, Nasta
AU  - Falk, Markus
AU  - Milašin, Jelena
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1862
AB  - Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P LT .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P LT .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.
T2  - Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
T1  - P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population
VL  - 125
IS  - 1
SP  - 52
EP  - 58
DO  - 10.1016/j.oooo.2017.09.013
ER  - 

@article{
author = "Nikolić, Nađa and Čarkić, Jelena and Ilić Dimitrijević, Ivana and Eljabo, Najib and Radunović, Milena and Aničić, Boban and Tanić, Nasta and Falk, Markus and Milašin, Jelena",
year = "2018",
abstract = "Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P LT .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P LT .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.",
journal = "Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology",
title = "P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population",
volume = "125",
number = "1",
pages = "52-58",
doi = "10.1016/j.oooo.2017.09.013"
}

Nikolić, N., Čarkić, J., Ilić Dimitrijević, I., Eljabo, N., Radunović, M., Aničić, B., Tanić, N., Falk, M.,& Milašin, J.. (2018). P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population. in Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 125(1), 52-58.
https://doi.org/10.1016/j.oooo.2017.09.013

Nikolić N, Čarkić J, Ilić Dimitrijević I, Eljabo N, Radunović M, Aničić B, Tanić N, Falk M, Milašin J. P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population. in Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2018;125(1):52-58.
doi:10.1016/j.oooo.2017.09.013 .

Nikolić, Nađa, Čarkić, Jelena, Ilić Dimitrijević, Ivana, Eljabo, Najib, Radunović, Milena, Aničić, Boban, Tanić, Nasta, Falk, Markus, Milašin, Jelena, "P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population" in Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 125, no. 1 (2018):52-58,
https://doi.org/10.1016/j.oooo.2017.09.013 . .

TY  - JOUR
AU  - Eljabo, Najib
AU  - Nikolić, Nađa
AU  - Čarkić, Jelena
AU  - Jelovac, Drago B.
AU  - Lazarević, Miloš M.
AU  - Tanić, Nasta
AU  - Milašin, Jelena
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0901502718300389
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7924
AB  - Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers. c-Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and p16 methylation status was determined by methylation-specific PCR (MSP PCR). All tissues examined exhibited molecular alterations in various proportions. Tumour tissues, as expected, showed the highest prevalence of alterations, while oral mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and tumour margins were significantly more frequent than in unaffected oral mucosa (P < 0.001 and P = 0.027, respectively). HER2 amplification in margin tissue (P < 0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in margins (P = 0.001) and macroscopically unaffected oral mucosa (P < 0.001) were correlated with shorter disease-specific survival.
T2  - International Journal of Oral and Maxillofacial Surgery
T1  - Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer
VL  - 47
IS  - 8
SP  - 976
EP  - 982
DO  - 10.1016/j.ijom.2018.01.020
ER  - 

@article{
author = "Eljabo, Najib and Nikolić, Nađa and Čarkić, Jelena and Jelovac, Drago B. and Lazarević, Miloš M. and Tanić, Nasta and Milašin, Jelena",
year = "2018",
abstract = "Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers. c-Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and p16 methylation status was determined by methylation-specific PCR (MSP PCR). All tissues examined exhibited molecular alterations in various proportions. Tumour tissues, as expected, showed the highest prevalence of alterations, while oral mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and tumour margins were significantly more frequent than in unaffected oral mucosa (P < 0.001 and P = 0.027, respectively). HER2 amplification in margin tissue (P < 0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in margins (P = 0.001) and macroscopically unaffected oral mucosa (P < 0.001) were correlated with shorter disease-specific survival.",
journal = "International Journal of Oral and Maxillofacial Surgery",
title = "Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer",
volume = "47",
number = "8",
pages = "976-982",
doi = "10.1016/j.ijom.2018.01.020"
}

Eljabo, N., Nikolić, N., Čarkić, J., Jelovac, D. B., Lazarević, M. M., Tanić, N.,& Milašin, J.. (2018). Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer. in International Journal of Oral and Maxillofacial Surgery, 47(8), 976-982.
https://doi.org/10.1016/j.ijom.2018.01.020

Eljabo N, Nikolić N, Čarkić J, Jelovac DB, Lazarević MM, Tanić N, Milašin J. Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer. in International Journal of Oral and Maxillofacial Surgery. 2018;47(8):976-982.
doi:10.1016/j.ijom.2018.01.020 .

Eljabo, Najib, Nikolić, Nađa, Čarkić, Jelena, Jelovac, Drago B., Lazarević, Miloš M., Tanić, Nasta, Milašin, Jelena, "Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer" in International Journal of Oral and Maxillofacial Surgery, 47, no. 8 (2018):976-982,
https://doi.org/10.1016/j.ijom.2018.01.020 . .

TY  - JOUR
AU  - Nikolić, Nađa
AU  - Aničić, Boban
AU  - Čarkić, Jelena
AU  - Simonovic, Jelena
AU  - Toljic, Bosko
AU  - Tanić, Nasta
AU  - Tepavcevic, Zvezdana
AU  - Vukadinovic, Miroslav
AU  - Konstantinovic, Vitomir S.
AU  - Milašin, Jelena
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/778
AB  - Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands. (C) 2015 Elsevier Ltd. All rights reserved.
T2  - Archives of Oral Biology
T1  - High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors
VL  - 60
IS  - 11
SP  - 1662
EP  - 1666
DO  - 10.1016/j.archoralbio.2015.08.011
ER  - 

@article{
author = "Nikolić, Nađa and Aničić, Boban and Čarkić, Jelena and Simonovic, Jelena and Toljic, Bosko and Tanić, Nasta and Tepavcevic, Zvezdana and Vukadinovic, Miroslav and Konstantinovic, Vitomir S. and Milašin, Jelena",
year = "2015",
abstract = "Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands. (C) 2015 Elsevier Ltd. All rights reserved.",
journal = "Archives of Oral Biology",
title = "High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors",
volume = "60",
number = "11",
pages = "1662-1666",
doi = "10.1016/j.archoralbio.2015.08.011"
}

Nikolić, N., Aničić, B., Čarkić, J., Simonovic, J., Toljic, B., Tanić, N., Tepavcevic, Z., Vukadinovic, M., Konstantinovic, V. S.,& Milašin, J.. (2015). High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. in Archives of Oral Biology, 60(11), 1662-1666.
https://doi.org/10.1016/j.archoralbio.2015.08.011

Nikolić N, Aničić B, Čarkić J, Simonovic J, Toljic B, Tanić N, Tepavcevic Z, Vukadinovic M, Konstantinovic VS, Milašin J. High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. in Archives of Oral Biology. 2015;60(11):1662-1666.
doi:10.1016/j.archoralbio.2015.08.011 .

Nikolić, Nađa, Aničić, Boban, Čarkić, Jelena, Simonovic, Jelena, Toljic, Bosko, Tanić, Nasta, Tepavcevic, Zvezdana, Vukadinovic, Miroslav, Konstantinovic, Vitomir S., Milašin, Jelena, "High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors" in Archives of Oral Biology, 60, no. 11 (2015):1662-1666,
https://doi.org/10.1016/j.archoralbio.2015.08.011 . .