Promoter Methylation of Specific Genes is Associated with the Phenotype and Progression of Colorectal Adenocarcinomas

Kim, Jin C.; Choi, Jin Sung; Roh, Seon Ae; Cho, Dong H.; Kim, Tae W.; Kim, Yong S.

doi:10.1245/s10434-009-0901-y

Cited by 79 publications

(54 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We observed DAPK methylation in 11.1% of the patients. This value is somewhat lower than previous reports for HNC (Nayak et al, 2007;Steinmann et al, 2009) but in concordance with the frequencies observed in colon (Kim et al, 2010) and breast cancer (Buyru et al, 2009), multiple myeloma (Galm et al, 2004;Braggio et al, 2010), and acute myeloid leukemia (Galm et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

Simultaneous Methylation Profiling of Tumor Suppressor Genes in Head and Neck Cancer

Yalnız

Demokan

Süoğlu

et al. 2011

DNA and Cell Biology

View full text Add to dashboard Cite

Head and neck cancer (HNC) is a common cancer, and its prognosis has not changed during the last decades. Detection of the disease at an early stage is crucial for successful treatment, as early diagnosis can significantly increase the survival rate. Methylation of tumor suppressor genes is an early event in cancer responsible for incorrect gene silencing. Since methylation changes are reversible, they also provide a promising target for therapy. So far, only individual genes have been analyzed for aberrant methylation in HNC. In this study, we analyzed the methylation status of 24 tumor suppressor genes simultaneously by methylation-specific multiplex ligation-dependent probe amplification in matched tumor and normal tissue samples from patients with HNC. CHFR, RARβ, DAPK1, and RASFF1 genes were the most frequently methylated genes in tumor tissue. Eight genes were not methylated in any sample. The methylation frequencies for individual genes ranged from 0% to 19%. Our results indicate that methylation of tumor suppressor genes is not high as previously reported by methylation-specific polymerase chain reaction and is confined to a smaller but significant fraction of the tumors. Whether this group represents a unique entity in the disease spectrum warrants further studies.

show abstract

Section: Discussionsupporting

confidence: 90%

Simultaneous Methylation Profiling of Tumor Suppressor Genes in Head and Neck Cancer

Yalnız

Demokan

Süoğlu

et al. 2011

DNA and Cell Biology

View full text Add to dashboard Cite

show abstract

“…The following electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945∼2014), the Cochrane Library Database (Issue 12, [27] 2011 Egypt 36 MSP Chen et al [28] 2 0 0 9 C h i n a 1 1 7 M S P Kim et al [29] 2010 Korea 570 Pyrosequencing Kohonen-Cosish et al [22] 2 0 0 5 A u s t r a l i a 1 8 3 M S P Krtolica et al [30] 2007 Belgrade 46 31.4 mo MSP Lee et al [31] 2 0 1 1 K o r e a 3 3 6 M S P Mokarram et al [32] 2 0 1 3 I r a n 9 2 M S P Nagasaka et al [6] 2 0 0 8 J a p a n 5 9 3 M S P Nagasaka et al [33] 2003 Japan 90 MSP Nilsson et al [7] 2013 Sweden 163 60 mo Pyrosequencing Shima et al [24] 2011 USA 124 156 mo q-MSP Sinha et al [34] 2013 India 855 2 mo MSP Zhang et al [25] 2011 China 24 23 mo MSP mo month, q-MSP quantitative methylation-specific PCR We searched articles using the following terms: MGMT promoter methylation and colorectal cancer or adenoma or normal tissue. We included studies that met the following criteria: (1) the association between MGMT methylation and CRC, and/or adenoma and (2) the association of MGMT methylation and prognosis in CRC patients.…”

Section: Articles Search Strategy and Selection Criteriamentioning

confidence: 99%

Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review

Li¹,

Lyu

Zhao

et al. 2015

Tumor Biol.

View full text Add to dashboard Cite

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

show abstract

“…[3][4][5] Additionally, APC is a CRC progression marker, 6 and its expression maybe downregulated in precancerous adenomatous tissue via promoter hypermethylation. 7 Likewise, 3OST2 is highly methylated (82%) in CRC, including sporadic and Lynch Syndrome CRC.…”

Section: Introductionmentioning

confidence: 99%

Toward a comprehensive and systematic methylome signature in colorectal cancers

et al. 2013

View full text Add to dashboard Cite

CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in colorectal cancer (CRC). This study aimed to define a methylome signature in CRC through a methylation microarray analysis and a compilation of promising CIMP markers from the literature. Illumina HumanMethylation27 (IHM27) array data was generated and analyzed based on statistical differences in methylation data (1st approach) or based on overall differences in methylation percentages using lower 95% CI (2nd approach). Pyrosequencing was performed for the validation of nine genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were hypermethylated in CRC but did not yet make it to the CIMP genes' list. Our 1st approach for array data analysis demonstrated the limitations in selecting genes for further validation, highlighting the need for the 2nd bioinformatics approach to adequately select genes with differential aberrant methylation. A more comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN, TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and TFPI2, was established. Array data are useful to categorize and cluster colonic lesions based on their global methylation profiles; however, its usefulness in identifying robust methylation markers is limited and rely on the data analysis method. We have identified 16 non-CIMP-panel genes for which we provide rationale for inclusion in a more comprehensive characterization of CIMP+ CRCs. The identification of a definitive list for methylome specific genes in CRC will contribute to better clinical management of CRC patients.

show abstract

Promoter Methylation of Specific Genes is Associated with the Phenotype and Progression of Colorectal Adenocarcinomas

Cited by 79 publications

References 38 publications

Simultaneous Methylation Profiling of Tumor Suppressor Genes in Head and Neck Cancer

Simultaneous Methylation Profiling of Tumor Suppressor Genes in Head and Neck Cancer

Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review

Toward a comprehensive and systematic methylome signature in colorectal cancers

Contact Info

Product

Resources

About