Molecular determinants for tumor marker design

Link to this page

info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173049/RS//

Molecular determinants for tumor marker design (en)
Молекуларне детерминанте за дизајн тумор маркера (sr)
Molekularne determinante za dizajn tumor markera (sr_RS)
Authors

Publications

Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels

Petrović, Nina; Davidović, Radoslav; Jovanović-Cupić, Snezana; Krajnović, Milena; Lukić, Silvana; Petrović, Milan; Roganović, Jelena

(Adis Int Ltd, Northcote, 2016)

TY  - JOUR
AU  - Petrović, Nina
AU  - Davidović, Radoslav
AU  - Jovanović-Cupić, Snezana
AU  - Krajnović, Milena
AU  - Lukić, Silvana
AU  - Petrović, Milan
AU  - Roganović, Jelena
PY  - 2016
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2120
AB  - Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3). The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors. In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan(A (R)) technology and immunohistochemistry. miR-221/222 levels varied significantly across groups based on invasiveness (P  lt  0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively). An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.
PB  - Adis Int Ltd, Northcote
T2  - Molecular Diagnosis & Therapy
T1  - Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels
VL  - 20
IS  - 6
SP  - 603
EP  - 615
DO  - 10.1007/s40291-016-0230-3
ER  - 
@article{
author = "Petrović, Nina and Davidović, Radoslav and Jovanović-Cupić, Snezana and Krajnović, Milena and Lukić, Silvana and Petrović, Milan and Roganović, Jelena",
year = "2016",
abstract = "Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3). The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors. In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan(A (R)) technology and immunohistochemistry. miR-221/222 levels varied significantly across groups based on invasiveness (P  lt  0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively). An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.",
publisher = "Adis Int Ltd, Northcote",
journal = "Molecular Diagnosis & Therapy",
title = "Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels",
volume = "20",
number = "6",
pages = "603-615",
doi = "10.1007/s40291-016-0230-3"
}
Petrović, N., Davidović, R., Jovanović-Cupić, S., Krajnović, M., Lukić, S., Petrović, M.,& Roganović, J.. (2016). Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels. in Molecular Diagnosis & Therapy
Adis Int Ltd, Northcote., 20(6), 603-615.
https://doi.org/10.1007/s40291-016-0230-3
Petrović N, Davidović R, Jovanović-Cupić S, Krajnović M, Lukić S, Petrović M, Roganović J. Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels. in Molecular Diagnosis & Therapy. 2016;20(6):603-615.
doi:10.1007/s40291-016-0230-3 .
Petrović, Nina, Davidović, Radoslav, Jovanović-Cupić, Snezana, Krajnović, Milena, Lukić, Silvana, Petrović, Milan, Roganović, Jelena, "Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels" in Molecular Diagnosis & Therapy, 20, no. 6 (2016):603-615,
https://doi.org/10.1007/s40291-016-0230-3 . .
1
12
10
12

Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component

Petrović, Nina; Jovanović-Cupić, Snezana; Brajušković, Goran; Lukić, Silvana; Roganović, Jelena; Krajnović, Milena; Mandusić, Vesna

(Srpsko biološko društvo, Beograd, i dr., 2015)

TY  - JOUR
AU  - Petrović, Nina
AU  - Jovanović-Cupić, Snezana
AU  - Brajušković, Goran
AU  - Lukić, Silvana
AU  - Roganović, Jelena
AU  - Krajnović, Milena
AU  - Mandusić, Vesna
PY  - 2015
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1991
AB  - Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (rho=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component
VL  - 67
IS  - 4
SP  - 1285
EP  - 1295
DO  - 10.2298/ABS150327105P
ER  - 
@article{
author = "Petrović, Nina and Jovanović-Cupić, Snezana and Brajušković, Goran and Lukić, Silvana and Roganović, Jelena and Krajnović, Milena and Mandusić, Vesna",
year = "2015",
abstract = "Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (rho=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component",
volume = "67",
number = "4",
pages = "1285-1295",
doi = "10.2298/ABS150327105P"
}
Petrović, N., Jovanović-Cupić, S., Brajušković, G., Lukić, S., Roganović, J., Krajnović, M.,& Mandusić, V.. (2015). Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 67(4), 1285-1295.
https://doi.org/10.2298/ABS150327105P
Petrović N, Jovanović-Cupić S, Brajušković G, Lukić S, Roganović J, Krajnović M, Mandusić V. Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component. in Archives of Biological Sciences. 2015;67(4):1285-1295.
doi:10.2298/ABS150327105P .
Petrović, Nina, Jovanović-Cupić, Snezana, Brajušković, Goran, Lukić, Silvana, Roganović, Jelena, Krajnović, Milena, Mandusić, Vesna, "Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component" in Archives of Biological Sciences, 67, no. 4 (2015):1285-1295,
https://doi.org/10.2298/ABS150327105P . .
2
2
2

Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia

Petrović, Nina; Mandusić, Vesna; Dimitrijević, Bogomir; Roganović, Jelena; Lukić, Silvana; Todorović, Lidija; Stanojević, Boban

(Humana Press Inc, Totowa, 2014)

TY  - JOUR
AU  - Petrović, Nina
AU  - Mandusić, Vesna
AU  - Dimitrijević, Bogomir
AU  - Roganović, Jelena
AU  - Lukić, Silvana
AU  - Todorović, Lidija
AU  - Stanojević, Boban
PY  - 2014
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1930
AB  - MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER? and PR? showed higher miR-21 levels than their negative receptor status paired groups ER-and PR-with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, rho = 0.379 and p = 0.034, rho = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy.
PB  - Humana Press Inc, Totowa
T2  - Medical Oncology
T1  - Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia
VL  - 31
IS  - 6
DO  - 10.1007/s12032-014-0977-5
ER  - 
@article{
author = "Petrović, Nina and Mandusić, Vesna and Dimitrijević, Bogomir and Roganović, Jelena and Lukić, Silvana and Todorović, Lidija and Stanojević, Boban",
year = "2014",
abstract = "MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER? and PR? showed higher miR-21 levels than their negative receptor status paired groups ER-and PR-with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, rho = 0.379 and p = 0.034, rho = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy.",
publisher = "Humana Press Inc, Totowa",
journal = "Medical Oncology",
title = "Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia",
volume = "31",
number = "6",
doi = "10.1007/s12032-014-0977-5"
}
Petrović, N., Mandusić, V., Dimitrijević, B., Roganović, J., Lukić, S., Todorović, L.,& Stanojević, B.. (2014). Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia. in Medical Oncology
Humana Press Inc, Totowa., 31(6).
https://doi.org/10.1007/s12032-014-0977-5
Petrović N, Mandusić V, Dimitrijević B, Roganović J, Lukić S, Todorović L, Stanojević B. Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia. in Medical Oncology. 2014;31(6).
doi:10.1007/s12032-014-0977-5 .
Petrović, Nina, Mandusić, Vesna, Dimitrijević, Bogomir, Roganović, Jelena, Lukić, Silvana, Todorović, Lidija, Stanojević, Boban, "Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia" in Medical Oncology, 31, no. 6 (2014),
https://doi.org/10.1007/s12032-014-0977-5 . .
10
14
12

The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion

Petrović, Nina; Mandusić, Vesna; Stanojević, Boban; Lukić, Silvana; Todorović, Lidija; Roganović, Jelena; Dimitrijević, Bogomir

(Humana Press Inc, Totowa, 2014)

TY  - JOUR
AU  - Petrović, Nina
AU  - Mandusić, Vesna
AU  - Stanojević, Boban
AU  - Lukić, Silvana
AU  - Todorović, Lidija
AU  - Roganović, Jelena
AU  - Dimitrijević, Bogomir
PY  - 2014
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1859
AB  - MicroRNA-21 (miR-21) overexpression is characteristic for various types of tumors, but it is still unknown whether its expression levels differ between invasive and non-invasive breast carcinomas. The main goal of the study was to determine the difference in miR-21 expression among normal tissue, non-invasive, invasive with non-invasive component, and pure invasive breast cancer samples, to explain its potential role and significance in breast cancer invasiveness. The second goal was to propose miR-21 as molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis. In order to reveal the role of miR-21 in breast cancer invasiveness, we measured miR-21 expression levels in 44 breast cancer and four normal samples by stem-loop real-time RT-PCR using TaqMan technology. Relative expression levels of miR-21 were significantly higher in invasive than in other groups (P = 0.002) and significantly higher in invasive compared with invasive with non-invasive component group in histological (P = 0.043) and nuclear grade 2 (P = 0.036), estrogen-receptor-positive (ER+) (P = 0.006), progesterone-receptor-positive (PR+) (P = 0.008), ER+ PR+ (P = 0.007), and proliferation index (Ki-67)  lt = 20 % (P = 0.036) tumors. Our findings suggest that miR-21 could be independent molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis.
PB  - Humana Press Inc, Totowa
T2  - Medical Oncology
T1  - The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion
VL  - 31
IS  - 3
DO  - 10.1007/s12032-014-0867-x
ER  - 
@article{
author = "Petrović, Nina and Mandusić, Vesna and Stanojević, Boban and Lukić, Silvana and Todorović, Lidija and Roganović, Jelena and Dimitrijević, Bogomir",
year = "2014",
abstract = "MicroRNA-21 (miR-21) overexpression is characteristic for various types of tumors, but it is still unknown whether its expression levels differ between invasive and non-invasive breast carcinomas. The main goal of the study was to determine the difference in miR-21 expression among normal tissue, non-invasive, invasive with non-invasive component, and pure invasive breast cancer samples, to explain its potential role and significance in breast cancer invasiveness. The second goal was to propose miR-21 as molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis. In order to reveal the role of miR-21 in breast cancer invasiveness, we measured miR-21 expression levels in 44 breast cancer and four normal samples by stem-loop real-time RT-PCR using TaqMan technology. Relative expression levels of miR-21 were significantly higher in invasive than in other groups (P = 0.002) and significantly higher in invasive compared with invasive with non-invasive component group in histological (P = 0.043) and nuclear grade 2 (P = 0.036), estrogen-receptor-positive (ER+) (P = 0.006), progesterone-receptor-positive (PR+) (P = 0.008), ER+ PR+ (P = 0.007), and proliferation index (Ki-67)  lt = 20 % (P = 0.036) tumors. Our findings suggest that miR-21 could be independent molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis.",
publisher = "Humana Press Inc, Totowa",
journal = "Medical Oncology",
title = "The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion",
volume = "31",
number = "3",
doi = "10.1007/s12032-014-0867-x"
}
Petrović, N., Mandusić, V., Stanojević, B., Lukić, S., Todorović, L., Roganović, J.,& Dimitrijević, B.. (2014). The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion. in Medical Oncology
Humana Press Inc, Totowa., 31(3).
https://doi.org/10.1007/s12032-014-0867-x
Petrović N, Mandusić V, Stanojević B, Lukić S, Todorović L, Roganović J, Dimitrijević B. The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion. in Medical Oncology. 2014;31(3).
doi:10.1007/s12032-014-0867-x .
Petrović, Nina, Mandusić, Vesna, Stanojević, Boban, Lukić, Silvana, Todorović, Lidija, Roganović, Jelena, Dimitrijević, Bogomir, "The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion" in Medical Oncology, 31, no. 3 (2014),
https://doi.org/10.1007/s12032-014-0867-x . .
1
41
29
44

TP53 and c-myc Co-alterations: A hallmark of oral cancer progression

Tanić, Nasta; Milašin, Jelena; Dramićanin, Tatjana; Bošković, Maja; Vukadinović, Miroslav; Milošević, Verica; Tanić, Nikola

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2013)

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milašin, Jelena
AU  - Dramićanin, Tatjana
AU  - Bošković, Maja
AU  - Vukadinović, Miroslav
AU  - Milošević, Verica
AU  - Tanić, Nikola
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1780
AB  - Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.
AB  - Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - TP53 and c-myc Co-alterations: A hallmark of oral cancer progression
T1  - Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma
VL  - 32
IS  - 4
SP  - 380
EP  - 388
DO  - 10.2478/jomb-2014-0009
ER  - 
@article{
author = "Tanić, Nasta and Milašin, Jelena and Dramićanin, Tatjana and Bošković, Maja and Vukadinović, Miroslav and Milošević, Verica and Tanić, Nikola",
year = "2013",
abstract = "Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours., Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "TP53 and c-myc Co-alterations: A hallmark of oral cancer progression, Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma",
volume = "32",
number = "4",
pages = "380-388",
doi = "10.2478/jomb-2014-0009"
}
Tanić, N., Milašin, J., Dramićanin, T., Bošković, M., Vukadinović, M., Milošević, V.,& Tanić, N.. (2013). TP53 and c-myc Co-alterations: A hallmark of oral cancer progression. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 32(4), 380-388.
https://doi.org/10.2478/jomb-2014-0009
Tanić N, Milašin J, Dramićanin T, Bošković M, Vukadinović M, Milošević V, Tanić N. TP53 and c-myc Co-alterations: A hallmark of oral cancer progression. in Journal of Medical Biochemistry. 2013;32(4):380-388.
doi:10.2478/jomb-2014-0009 .
Tanić, Nasta, Milašin, Jelena, Dramićanin, Tatjana, Bošković, Maja, Vukadinović, Miroslav, Milošević, Verica, Tanić, Nikola, "TP53 and c-myc Co-alterations: A hallmark of oral cancer progression" in Journal of Medical Biochemistry, 32, no. 4 (2013):380-388,
https://doi.org/10.2478/jomb-2014-0009 . .
3
3
3