Effects of X-ray irradiation on methylation levels of p16, MGMT and APC genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa

Krakowczyk, Łukasz; Strzelczyk, Joanna Katarzyna; Blamek, Sławomir; Maciejewski, Adam; Półtorak, Stanisław; Wiczkowski, Andrzej

doi:10.1186/1897-4287-10-s3-a12

Cited by 14 publications

(14 citation statements)

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“…This is in agreement with some previous reports of an age-related methylation of tumor suppressor genes in normal colorectal mucosa, that might represent physiological changes and/or constitute pre-neoplastic lesions. 20,21 The MGMT gene is involved in DNA repair processes (mismatch repair) and in our cohort resulted hypermethylated in more than 40% of CRC tissues and in 17.5% of normal colonic mucosa. Again, we observed higher methylation levels in the affected tissue than in the adjacent healthy mucosa.…”

Section: Discussionmentioning

confidence: 65%

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

et al. 2014

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Section: Discussionmentioning

confidence: 65%

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

et al. 2014

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“…There are a variety of DNA repair mechanisms in cells that play essential roles in the prevention of gene mutations and the maintenance of genomic integrity and stability [1,2]. The enhanced expressions of DNA damage repair genes have been shown to decrease the chemotherapeutic sensitivity of cancers because most chemotherapeutic agents target the DNA damage pathways [3,4].…”

Section: Introductionmentioning

confidence: 99%

Increased expression of DNA repair gene XPF enhances resistance to hydroxycamptothecin in bladder cancer

Zhang

Liu

et al. 2012

Med Sci Monit

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SummaryBackgroundXeroderma pigmentosum group F (XPF) is an important participant in the nucleotide excision repair process. This study aimed to investigate the expression of DNA repair gene xeroderma pigmentosum group F (XPF) in bladder cancer and its clinical significance.Material/MethodsTotal RNA and protein were extracted from 45 untreated bladder cancer tissues and 21 hydroxycamptothecin (HCPT)-treated bladder cancer specimens. Real-time PCR and Western blot assay were used to detect the mRNA and protein levels of XPF, respectively. siRNA targeting XPF was used to knock down the XPF expression in T24 cells and 5637 cells, and the sensitivity of XPF-depleted cells to HCPT was measured.ResultsThe XPF expressions in the HCPT-treated cancer tissues was significantly higher than those in the untreated cancer tissues at both mRNA and protein levels. Importantly, the enhanced XPF expression decreased the sensitivity of T24 cells and 5637 cells to HCPT. Furthermore, the HCPT treatment significantly increased the apoptosis of T24 cells and 5637 cells. Alternatively, after the XPF gene silencing, the chemotherapeutic resistance of bladder cancer cells was significantly decreased.ConclusionsOur results show the increased expression of XPF is involved in the chemotherapeutic resistance of bladder cancer, and decreasing XPF expression may become a promising therapeutic strategy for bladder cancer.

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“…However, several studies identified a prognostic role for promoter methylation of genes not included in the CpG island hypermethylation panel such as MGMT, RASSF1A, or BAGE. [23][24][25] Nevertheless, none of these markers has yet found its clinical application.…”

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confidence: 99%

Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1

et al. 2014

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Surgical excision of colorectal cancer at early clinical stages is highly effective, but 20-30% of patients relapse. Therefore, it is of clinical relevance to identify patients at high risk for recurrence, who would benefit from adjuvant chemotherapy. The objective of this study was to identify prognostic and/or predictive methylation markers in stage II colorectal cancer patients. Therefore, we selected six gene promoters (FZD9, PCDH10 (protocadherin 10), SFRP2, SPARC (secreted protein acidic and rich in cysteine), UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), and WIF1) for methylation analysis in formalin-fixed, paraffin-embedded primary tumor samples of colorectal cancer patients (n ¼ 143) who were enrolled in a prospective randomized phase III trial of the Austrian Breast and Colorectal cancer Study Group. Patients were randomized to adjuvant chemotherapy with 5-fluorouracil and leucovorin or surveillance only. Survival analyses revealed that combined evaluation of three promoters (PCDH10, SPARC, and UCHL1) showed differential effects with regard to disease-free survival and overall survival in the two treatment groups (significance level 0.007). In the chemotherapy arm, a statistically insignificant trend for patients without methylation toward longer survival was observed (P ¼ 0.069 for disease-free survival and P ¼ 0.139 for overall survival). Contrary, patients in the surveillance arm without methylation in their gene promoters had shorter disease-free survival and overall survival (P ¼ 0.031 for disease-free survival and P ¼ 0.003 for overall survival), indicating a prognostic effect of methylation in this group (test for interaction, P ¼ 0.006 for disease-free survival and P ¼ 0.018 for overall survival). These results indicate that promoter methylation status of PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients and, therefore, may facilitate treatment decisions for stage II colorectal cancer.

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Effects of X-ray irradiation on methylation levels of p16, MGMT and APC genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa

Cited by 14 publications

References 0 publications

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

Increased expression of DNA repair gene XPF enhances resistance to hydroxycamptothecin in bladder cancer

Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1

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