Hypermethylation of promoter regions of the APC1A and p16INK4a genes in relation to prognosis and tumor characteristics in cervical cancer patients
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Hypermethylation of promoter regions of the APC1A and p16INK4a genes in relation to prognosis and tumor characteristics in cervical cancer patients. / Öhlin, Zarah Maria Löf; Sorbe, Bengt; Wingren, Sten; Nilsson, Torbjörn K.
In: International Journal of Oncology Research, Vol. 39, No. 3, 09.2011, p. 683-8.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Hypermethylation of promoter regions of the APC1A and p16INK4a genes in relation to prognosis and tumor characteristics in cervical cancer patients
AU - Öhlin, Zarah Maria Löf
AU - Sorbe, Bengt
AU - Wingren, Sten
AU - Nilsson, Torbjörn K
PY - 2011/9
Y1 - 2011/9
N2 - Hypermethylation of the O6-MGMT, p14ARF, p16INK4a, RASSF1A and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer. Methylation was studied in DNA extracts from surgical specimens of cancer tissue by novel pyrosequencing methods. In 109 patients (90 squamous cell carcinomas, 19 adenocarcinomas), we found that hypermethylation of the APC1A gene promoter occurred in 8.3% of patients, and of p16INK4a in 1.8%. APC1A hypermethylation was significantly related to more advanced FIGO stage of the tumor (P=0.013), larger tumor diameter (P=0.049) and distant recurrence-free survival (P=0.0007), but not with locoregional recurrence rate, age, HPV status, DNA ploidy, tumor grade or malignancy grading score. We conclude that methylation of the APC1A promoter in cervical cancer, as diagnosed by pyrosequencing, is significantly related to major biological characteristics of the tumor, and may be a new predictor of poor prognosis in cervical cancer.
AB - Hypermethylation of the O6-MGMT, p14ARF, p16INK4a, RASSF1A and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer. Methylation was studied in DNA extracts from surgical specimens of cancer tissue by novel pyrosequencing methods. In 109 patients (90 squamous cell carcinomas, 19 adenocarcinomas), we found that hypermethylation of the APC1A gene promoter occurred in 8.3% of patients, and of p16INK4a in 1.8%. APC1A hypermethylation was significantly related to more advanced FIGO stage of the tumor (P=0.013), larger tumor diameter (P=0.049) and distant recurrence-free survival (P=0.0007), but not with locoregional recurrence rate, age, HPV status, DNA ploidy, tumor grade or malignancy grading score. We conclude that methylation of the APC1A promoter in cervical cancer, as diagnosed by pyrosequencing, is significantly related to major biological characteristics of the tumor, and may be a new predictor of poor prognosis in cervical cancer.
KW - Adaptor Proteins, Signal Transducing
KW - Cyclin-Dependent Kinase Inhibitor p16
KW - DNA Methylation
KW - DNA Modification Methylases
KW - DNA Repair Enzymes
KW - Disease-Free Survival
KW - Epigenomics
KW - Female
KW - Humans
KW - Prognosis
KW - Promoter Regions, Genetic
KW - Tumor Suppressor Proteins
KW - Uterine Cervical Neoplasms
U2 - 10.3892/ijo.2011.1078
DO - 10.3892/ijo.2011.1078
M3 - Journal article
C2 - 21674126
VL - 39
SP - 683
EP - 688
JO - International Journal of Oncology Research
JF - International Journal of Oncology Research
IS - 3
ER -
ID: 46848137