TY  - CONF
AU  - Ademović, Nejla
AU  - Tomić, Tijana
AU  - Tanić, Nasta
AU  - Milić, Marina
AU  - Rakić, Miodrag
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6234
AB  - Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Genomic instability as a prognostic marker in malignant brain cancer
SP  - 90
EP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6234
ER  - 

@conference{
author = "Ademović, Nejla and Tomić, Tijana and Tanić, Nasta and Milić, Marina and Rakić, Miodrag and Tanić, Nikola",
year = "2023",
abstract = "Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Genomic instability as a prognostic marker in malignant brain cancer",
pages = "90-91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6234"
}

Ademović, N., Tomić, T., Tanić, N., Milić, M., Rakić, M.,& Tanić, N.. (2023). Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234

Ademović N, Tomić T, Tanić N, Milić M, Rakić M, Tanić N. Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

Ademović, Nejla, Tomić, Tijana, Tanić, Nasta, Milić, Marina, Rakić, Miodrag, Tanić, Nikola, "Genomic instability as a prognostic marker in malignant brain cancer" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):90-91,
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

TY  - JOUR
AU  - Milinković, Vedrana P.
AU  - Banković, Jasna Z.
AU  - Rakić, Miodrag L
AU  - Stanković, Tijana
AU  - Skender-Gazibara, Milica K
AU  - Ruždijić, Sabera
AU  - Tanić, Nikola T
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/938
AB  - Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.
T2  - Plos One
T1  - Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients
IS  - 12
VL  - 8
SP  - 977
EP  - na
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_938
ER  - 

@article{
author = "Milinković, Vedrana P. and Banković, Jasna Z. and Rakić, Miodrag L and Stanković, Tijana and Skender-Gazibara, Milica K and Ruždijić, Sabera and Tanić, Nikola T",
year = "2013",
abstract = "Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.",
journal = "Plos One",
title = "Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients",
number = "12",
volume = "8",
pages = "977-na",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_938"
}

Milinković, V. P., Banković, J. Z., Rakić, M. L., Stanković, T., Skender-Gazibara, M. K., Ruždijić, S.,& Tanić, N. T.. (2013). Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients. in Plos One, 8(12), 977-na.
https://hdl.handle.net/21.15107/rcub_ibiss_938

Milinković VP, Banković JZ, Rakić ML, Stanković T, Skender-Gazibara MK, Ruždijić S, Tanić NT. Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients. in Plos One. 2013;8(12):977-na.
https://hdl.handle.net/21.15107/rcub_ibiss_938 .

Milinković, Vedrana P., Banković, Jasna Z., Rakić, Miodrag L, Stanković, Tijana, Skender-Gazibara, Milica K, Ruždijić, Sabera, Tanić, Nikola T, "Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients" in Plos One, 8, no. 12 (2013):977-na,
https://hdl.handle.net/21.15107/rcub_ibiss_938 .

TY  - JOUR
AU  - Milinković, Vedrana P.
AU  - Banković, Jasna Z.
AU  - Rakić, Miodrag L
AU  - Milosević, Nebojsa T
AU  - Stanković, Tijana
AU  - Joković, Milos B
AU  - Milošević, Zorica Z.
AU  - Skender-Gazibara, Milica K
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Ruždijić, Sabera
AU  - Tanić, Nikola T
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1108
AB  - The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved.
T2  - Experimental and Molecular Pathology
T1  - Genomic instability and p53 alterations in patients with malignant glioma
IS  - 2
VL  - 93
SP  - 67
EP  - 206
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1108
ER  - 

@article{
author = "Milinković, Vedrana P. and Banković, Jasna Z. and Rakić, Miodrag L and Milosević, Nebojsa T and Stanković, Tijana and Joković, Milos B and Milošević, Zorica Z. and Skender-Gazibara, Milica K and Podolski-Renić, Ana and Pešić, Milica and Ruždijić, Sabera and Tanić, Nikola T",
year = "2012",
abstract = "The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved.",
journal = "Experimental and Molecular Pathology",
title = "Genomic instability and p53 alterations in patients with malignant glioma",
number = "2",
volume = "93",
pages = "67-206",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1108"
}

Milinković, V. P., Banković, J. Z., Rakić, M. L., Milosević, N. T., Stanković, T., Joković, M. B., Milošević, Z. Z., Skender-Gazibara, M. K., Podolski-Renić, A., Pešić, M., Ruždijić, S.,& Tanić, N. T.. (2012). Genomic instability and p53 alterations in patients with malignant glioma. in Experimental and Molecular Pathology, 93(2), 67-206.
https://hdl.handle.net/21.15107/rcub_ibiss_1108

Milinković VP, Banković JZ, Rakić ML, Milosević NT, Stanković T, Joković MB, Milošević ZZ, Skender-Gazibara MK, Podolski-Renić A, Pešić M, Ruždijić S, Tanić NT. Genomic instability and p53 alterations in patients with malignant glioma. in Experimental and Molecular Pathology. 2012;93(2):67-206.
https://hdl.handle.net/21.15107/rcub_ibiss_1108 .

Milinković, Vedrana P., Banković, Jasna Z., Rakić, Miodrag L, Milosević, Nebojsa T, Stanković, Tijana, Joković, Milos B, Milošević, Zorica Z., Skender-Gazibara, Milica K, Podolski-Renić, Ana, Pešić, Milica, Ruždijić, Sabera, Tanić, Nikola T, "Genomic instability and p53 alterations in patients with malignant glioma" in Experimental and Molecular Pathology, 93, no. 2 (2012):67-206,
https://hdl.handle.net/21.15107/rcub_ibiss_1108 .