Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis

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dc.catalogadoryvc
dc.contributor.authorTakahashi, Takao
dc.contributor.authorShivapurkar, Narayan
dc.contributor.authorRiquelme Sánchez, Erick Marcelo
dc.contributor.authorShigematsu, Hisayuki
dc.contributor.authorReddy, Jyotsna
dc.contributor.authorSuzuki, Makoto
dc.contributor.authorMiyajima, Kuniharu
dc.contributor.authorZhou, Xian
dc.contributor.authorBekele, B. Nebiyou
dc.contributor.authorGazdar, Adi F.
dc.contributor.authorWistuba Oyarzún, Ignacio
dc.date.accessioned2024-07-18T13:59:46Z
dc.date.available2024-07-18T13:59:46Z
dc.date.issued2004
dc.description.abstractPurpose: Aberrant methylation of 5' gene promoter regions is an epigenetic phenomenon that is a major mechanism for silencing of tumor suppressor genes in many cancer types. There is limited information about the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC), including methylation status. Experimental Design: We investigated the aberrant promoter methylation profile of 24 known or suspected tumor suppressor genes in 50 GBCs and compared those results with the findings in 25 chronic cholecystitis (CC) specimens without cancer. The methylation-specific polymerase chain reaction and combined restriction analysis methods were used to detect methylation, and the results were confirmed by sequencing of cloned polymerase chain reaction products. Results: In GBC, gene methylation frequencies varied from 0% to 80%. Ten genes demonstrated relatively high frequencies of aberrant methylation: SHP1 (80%), 3-OST-2 (72%), CDH13 (44%), P-15(INK4B) (44%), CDH1 (38%), RUNX3 (32%), APC (30%), RIZ1 (26%), P16(INK4A) (24%), and HPP1 (20 %). Eight genes (P73, RARbeta2, SOCS-1, DAPK, DcR2, DcR1, HIN1, and CHFR) showed low frequencies (2-14%) of methylation, and no methylation of the remaining six genes (TIMP-3, P57, RASSF1A, CRBP1, SYK, and NORE1) was detected. In CC, methylation was detected for seven genes: SHP1 (88 %), P15(INK4B) (28 %), 3-OST-2 (12%), CDH1 (12 %), CDH13 (8 %), DcR2 (4 %), and P16(INK4A) (4%) Significantly higher frequencies of methylation in GBC compared with CC were detected for eight genes (3-OST-2, CDH13, CDH1, RUNX3, APC, RIZ1, P16(INK4A), and HPP1). Of those, four genes showed frequent methylation (>30%) in GBCs. The mean methylation index, an expression of the amount of methylated genes by case, was significantly higher in GBC (0.196 +/- 0.013) compared with CC (0.065 +/- 0.008; P < 0.001). Conclusions: Our study constitutes the most comprehensive methylation profile report available in GBC and demonstrates that this neoplasm has a distinct pattern of abnormal gene methylation. Whereas gallbladders from healthy individual were not available, our finding of methylation in CC cases without cancer suggests that this phenomenon represents an early event in the pathogenesis of GBC.
dc.description.funderANID FONDECYT No. 1020960
dc.fechaingreso.objetodigital2024-07-18
dc.format.extent8 páginas
dc.fuente.origenWoS
dc.identifier.doi10.1158/1078-0432.CCR-04-0579
dc.identifier.eissn1557-3265
dc.identifier.issn1078-0432
dc.identifier.pubmedidMEDLINE_ID: 15447999
dc.identifier.urihttps://doi.org/10.1158/1078-0432.CCR-04-0579
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87104
dc.identifier.wosidWoS_ID: 000224080200021
dc.information.autorucEscuela de Medicina; Riquelme Sánchez, Erick Marcelo; 0000-0002-2696-7995; 1001194
dc.information.autorucS/I; Wistuba Oyarzún, Ignacio; S/I; 100278
dc.issue.numero18
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final6133
dc.pagina.inicio6126
dc.publisherAmerican Association Cancer Research
dc.revistaClinical Cancer Research
dc.rightsacceso restringido
dc.subjectCarcinoma
dc.subjectTumor-Suppresor Gene
dc.subjectHuman Breast-Cancer
dc.subjectChronic Disease
dc.subjectDNA Methylation
dc.subjectLung
dc.subjectCell Differentiation
dc.subjectPathogenesis
dc.subjectSulfites
dc.subjectGallbladder Neoplasms
dc.subjectPromoter Regions (Genetics)
dc.subjectCholecystitis
dc.subject.ddc610
dc.titleAberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis
dc.typeartículo
dc.volumen10
sipa.codpersvinculados1001194
sipa.codpersvinculados100278
sipa.trazabilidadWoS;05-06-2021
sipa.trazabilidadORCID;2024-07-14
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