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DNA methylation of the p14(ARF), RASSF1A and APC1A genes as an independent prognostic factor in colorectal cancer patients
Örebro University Hospital, Sweden University of Örebro, Sweden .
Örebro University Hospital, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
2013 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 42, no 1, 127-133 p.Article in journal (Refereed) Published
Abstract [en]

We quantitated the methylated fraction of CpG sites in the promoter regions of O-6-MGMT, p14(ARF), p16(INK4a), RASSF1A and APC1A in tumor tissue from patients with colorectal cancer (CRC) in order to determine if promoter hypermethylation of any of these genes predicts survival. DNA was isolated from 111 primary CRC and 46 matched normal colorectal mucosa samples from the same patients, obtained at primary surgery and DNA methylation was examined by Pyrosequencing (R). Follow-up time was up to 20 years. Patients showed partial promoter methylation in the following frequencies: O-6-MGMT, 34%; p14(ARF), 29%; p16(INK4a), 28%; RASSF1A, 14%; and APC1A, 27%. Normal mucosa was always unmethylated. CRC patients with methylated p14(ARF). gene promoter had significantly worse prognosis (p=0.036), whereas those with methylated O-6-MGMT had significantly better prognosis through the first 60 months post-treatment (RR 0.36; p=0.023). Methylation of one or more of the genes from the set p14(ARF), RASSF1A and APC1A, was significantly (p=0.021) associated with worse prognosis even adjusting for tumor stage and differentiation (RR 2.2, p=0.037). Thus, DNA methylation of the p14(ARF), RASSF1A and APC1A genes, diagnosed by Pyrosequencing, defines a poor prognosis subset of CRC patients independently of both tumor stage and differentiation. O-6-MGMT methylation may play a protective role.

Place, publisher, year, edition, pages
Spandidos Publications , 2013. Vol. 42, no 1, 127-133 p.
Keyword [en]
APC1A, colorectal cancer, CpG sites, DNA methylation, O-6-MGMT, p14(ARF), p16(INK4a), preterapeutic predictor, prognosis, Pyrosequencing (R), RASSF1A, survival, tumor stage, tumor differentiation
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-87460DOI: 10.3892/ijo.2012.1682ISI: 000312566900014OAI: diva2:589484

Funding Agencies|Orebro County Council, Nyckelfonden, Orebro||Lions Cancerfond, Uppsala||

Available from: 2013-01-18 Created: 2013-01-18 Last updated: 2013-01-18

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Sun, Xiao-Feng
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OncologyFaculty of Health SciencesDepartment of Oncology UHL
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