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RISS 인기검색어
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- 저자 : ( Otgontuya Sambuudash ) (검색결과 2 건)
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Lack of Aberrant Methylation in an Adjacent Area of Left-Sided Colorectal Cancer
Otgontuya Sambuudash,김현수,조미연 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.4
Purpose: The molecular nature and the rate-limiting step of epigenetic field defects in the evolution of left-sided colorectal cancer (LCA) remain uncertain. Materials and Methods: The methylation status of 27 candidate field defect markers, six classic CpG island methylator phenotype (CIMP) markers, and LINE-1 were determined in LCA and adjacent normal mucosas (ADJs) from 33 LCA patients and in left normalcolorectal mucosa (LNM) from 33 age- and sex-matched controls. Hotspot mutation analyses in KRAS codons 12 and 13 and BRAF V600E were performed by genomic PCR and pyrosequencing using DNA extracted from endoscopically biopsied tissues. Results: Among the 27 candidate genes tested, we confirmed 15 differentially methylated genes in cancer (15 DMGs; ER, SFRP1, MYOD1, MGMT, CD8a, SPOCK2, ABHD9, BNIP3, IGFBP3, WIF1, MAL, GDNF, ALX4, DOK5, and SLC16A12) in comparison to ADJ samples. We further compared the methylation status of 15 DMGs of ADJs to LNM and found only methylation levels of SLC16A12in ADJs of LCA patients to be significantly higher than that in LNM (17.3% vs. 11.5%, p=0.002). Based on the CIMP, no significantdifferences in methylation levels of the 15 DMGs were found between ADJs in CIMP positive LCA cases and those withoutCIMP. In mutation analyses, no mutation was found in ADJs, while significant KRAS mutations (6/33, 18%) were noted in LCA samples. Conclusion: Epigenetic field defect marked by aberrant methylation is uncommon in normal-appearing ADJs of LCA, indicating the critical rate-limiting change of methylation is likely to occur with morphological alterations in the evolution of LCA.
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( Hyun Sik Kim ),( Hee Man Kim ),( Otgontuya Sambuudash ),( Hannah Jo ),( Kyung Ju Lee ),( Hong Jun Park ),( Jae Woo Kim ),( Mee Yon Cho ),( Hyun Soo Kim ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: As one of the colorectal cancer carcinogenesis, serrated neoplasia pathway is characterized with BRAF mutation and aberrant DNA methylation. Methods: Between 2005 and 2013, 146 colon polyps (47 tubular adenoma [TA], 53 traditional serrated adenoma [TSA], 17 sessile serrated adenoma/polyp [SSA] and 29 hyperplastic polyps in proximal colon [PHP] were collected in Yonsei University Wonju College of Medicine. The paraffi n embedded tissues of colon polyps were deparaffi nized, DNA was extracted, and polymerase chain reaction (PCR) was performed. BRAF V600E mutation was identifi ed through PCR and pyrosequencing assay, and methylationof LINE-1, IGFBP7, hMLH1, and CD133 was evaluated through disulfi te conversion, PCR, and pyrosequencing assay. Results: BRAF V600E mutation was found in 2.1% of TA, 47.2% of TSA, 41.2% of SSA, and 20.7% of HP. TSA and SSA had higher BRAF mutation than TA (P<0.0001). TSA had higher BRAF mutation than HP (P=0.018). IGFBP7 hypermethylation was found in 17% of TA, 37.7% of TSA, 88.2% of SSA, and 37.5% of HP. TSA and SSA had higher hypermethylation of IGFBP7 than TA (P=0.021 and P<0.0001, respectively). SSA had higher hypermethylation of IGFBP7 than HP (P=0.002). hMLH1 hypermethylation was found in 2.1% of TA, 5.7% of TSA, 0% of SSA, and 0% of HP. CD133 hypermethylation was found in 21.3% of TA, 9.4% of TSA, 35.3% of SSA, and 17.4 % of HP. Conclusions: TSA and SSA have different expression of BRAF V600E mutation and IGFBP7 hypermethylation as compared to TA. HP in proximal colon had different expression of BRAF mutation from TSA, and IGFBP7 hypermethylation from SSA. These fi ndings suggest that TSA and SSA have different genetic alterations from TA or HP.
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