Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value
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Autori
Krtolica-Žikić, KoviljkaKrajnović, Milena M.
Usaj-Knežević, Slavica
Babić, Dragan
Jovanovic, Dusan
Dimitrijević, Bogomir B.
Članak u časopisu
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Prikaz svih podataka o dokumentuApstrakt
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 comethylat...ion 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.
Ključne reči:
colorectal carcinoma / DNA methylation / p16 / MGMT / K-ras mutationIzvor:
World Journal of Gastroenterology, 2007, 13, 8, 1187-1194
DOI: 10.3748/wjg.v13.i8.1187
ISSN: 1007-9327
PubMed: 17451198
WoS: 000245577500007
Scopus: 2-s2.0-34247129670
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Institucija/grupa
VinčaTY - 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 . .