TY  - JOUR
AU  - Krtolica-Žikić, Koviljka
AU  - Krajnović, Milena M.
AU  - Usaj-Knežević, Slavica
AU  - Babić, Dragan
AU  - Jovanovic, Dusan
AU  - Dimitrijević, Bogomir B.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3184
AB  - AIM: To investigate the significance of p16 and O-6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCS, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P LT 0.05, chi(2)-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 +/- 6.0 mo vs 23.1 +/- 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P LT 0.001, chi(2)-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 +/- 1.9 mo vs 37.0 +/- 1.8 mo, P LT 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis. (C) 2007 The WJG Press. All rights reserved.
T2  - World Journal of Gastroenterology
T1  - Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value
VL  - 13
IS  - 8
SP  - 1187
EP  - 1194
DO  - 10.3748/wjg.v13.i8.1187
ER  - 

@article{
author = "Krtolica-Žikić, Koviljka and Krajnović, Milena M. and Usaj-Knežević, Slavica and Babić, Dragan and Jovanovic, Dusan and Dimitrijević, Bogomir B.",
year = "2007",
abstract = "AIM: To investigate the significance of p16 and O-6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCS, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P LT 0.05, chi(2)-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 +/- 6.0 mo vs 23.1 +/- 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P LT 0.001, chi(2)-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 +/- 1.9 mo vs 37.0 +/- 1.8 mo, P LT 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis. (C) 2007 The WJG Press. All rights reserved.",
journal = "World Journal of Gastroenterology",
title = "Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value",
volume = "13",
number = "8",
pages = "1187-1194",
doi = "10.3748/wjg.v13.i8.1187"
}

Krtolica-Žikić, K., Krajnović, M. M., Usaj-Knežević, S., Babić, D., Jovanovic, D.,& Dimitrijević, B. B.. (2007). Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value. in World Journal of Gastroenterology, 13(8), 1187-1194.
https://doi.org/10.3748/wjg.v13.i8.1187

Krtolica-Žikić K, Krajnović MM, Usaj-Knežević S, Babić D, Jovanovic D, Dimitrijević BB. Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value. in World Journal of Gastroenterology. 2007;13(8):1187-1194.
doi:10.3748/wjg.v13.i8.1187 .

Krtolica-Žikić, Koviljka, Krajnović, Milena M., Usaj-Knežević, Slavica, Babić, Dragan, Jovanovic, Dusan, Dimitrijević, Bogomir B., "Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value" in World Journal of Gastroenterology, 13, no. 8 (2007):1187-1194,
https://doi.org/10.3748/wjg.v13.i8.1187 . .