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 . .

TY  - JOUR
AU  - Nikolic, Nada
AU  - Aničić, Boban
AU  - Tepavcevic, Zvezdana
AU  - Jezdic, Zoran
AU  - Čarkić, Jelena
AU  - Toljic, Bosko
AU  - Dedović-Tanić, Nasta
AU  - Konstantinovic, Vitomir
AU  - Vukadinovic, Miroslav
AU  - Milašin, Jelena
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5746
AB  - Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomorphic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detection). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p LT 0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c-myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter polymorphisms represent susceptibility factors for the development of PAs in the Serbian population.
T2  - Journal of Medical Biochemistry
T1  - Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands
VL  - 32
IS  - 4
SP  - 354
EP  - 360
DO  - 10.2478/jomb-2013-0048
ER  - 

@article{
author = "Nikolic, Nada and Aničić, Boban and Tepavcevic, Zvezdana and Jezdic, Zoran and Čarkić, Jelena and Toljic, Bosko and Dedović-Tanić, Nasta and Konstantinovic, Vitomir and Vukadinovic, Miroslav and Milašin, Jelena",
year = "2013",
abstract = "Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomorphic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detection). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p LT 0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c-myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter polymorphisms represent susceptibility factors for the development of PAs in the Serbian population.",
journal = "Journal of Medical Biochemistry",
title = "Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands",
volume = "32",
number = "4",
pages = "354-360",
doi = "10.2478/jomb-2013-0048"
}

Nikolic, N., Aničić, B., Tepavcevic, Z., Jezdic, Z., Čarkić, J., Toljic, B., Dedović-Tanić, N., Konstantinovic, V., Vukadinovic, M.,& Milašin, J.. (2013). Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands. in Journal of Medical Biochemistry, 32(4), 354-360.
https://doi.org/10.2478/jomb-2013-0048

Nikolic N, Aničić B, Tepavcevic Z, Jezdic Z, Čarkić J, Toljic B, Dedović-Tanić N, Konstantinovic V, Vukadinovic M, Milašin J. Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands. in Journal of Medical Biochemistry. 2013;32(4):354-360.
doi:10.2478/jomb-2013-0048 .

Nikolic, Nada, Aničić, Boban, Tepavcevic, Zvezdana, Jezdic, Zoran, Čarkić, Jelena, Toljic, Bosko, Dedović-Tanić, Nasta, Konstantinovic, Vitomir, Vukadinovic, Miroslav, Milašin, Jelena, "Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands" in Journal of Medical Biochemistry, 32, no. 4 (2013):354-360,
https://doi.org/10.2478/jomb-2013-0048 . .