Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma

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dc.contributor.authorRiquelme, Erick
dc.contributor.authorTang, Moying
dc.contributor.authorBaez, Sergio
dc.contributor.authorDiaz, Alfonso
dc.contributor.authorPruyas, Martha
dc.contributor.authorWistuba, Ignacio I.
dc.contributor.authorCorvalan, Alejandro
dc.date.accessioned2024-01-10T13:48:35Z
dc.date.available2024-01-10T13:48:35Z
dc.date.issued2007
dc.description.abstractGallbladder carcinoma (GBC) is a highly malignant neoplasm that represents the leading cause of death for cancer in Chilean females. There is limited information about the molecular abnormalities involved in its pathogenesis. We have identified a number of molecular changes in GBC, including frequent allelic losses at chromosome 3p regions. Four distinct 3p sites (3p12, 3p14.2, 3p21.3 and 3p22-24) with frequent and early allelic losses in the sequential pathogenesis of this neoplasm have been detected. We investigated epigenetic and genetic abnormalities in GBC affecting 6 candidate tumor suppressor genes (TSG) located in chromosome 3p, including DUTT1 (3p12), FHIT(3p14.2), BLU, RASSF1A, SEMA3B and hMLH1 (3p21.3). DNA extracted from frozen tissue obtained from 50 surgical resected GBCs was examined for gene promoter methylation using MSP (methylation-specific PCR) technique after bisulfite treatment in all 6 genes. In addition, we performed PCR-based mutation examination using SSCP in FHIT and RASSF1A genes and loss of heterozygosity (LOH) analysis using microdissected tissue in a subset of tumors for the 3p21.3 region with 8 microsatellite markers. A very high frequency of GBC methylation was detected in SEMA3B (46/50, 92%) and FHIT (33/50, 66%), inter-mediate incidences in BLU (13/50, 26%) and DUTT1 (11/50, 22%) and very low frequencies in RASSF1A (4/50, 8%) and hMLH1 (2/50, 4%). Allelic loss at 3p21.3 was found in nearly half of the GBCs examined. We conclude that epigenetic inactivation by abnormal promoter methylation is a frequent event in chromosome 3p candidate TSGs in GBC pathogenesis, especially affecting genes SEMA3B (3p21.3) and FHIT (3p 14.2). (c) 2006 Elsevier Ireland Ltd. All rights reserved.
dc.fechaingreso.objetodigital21-03-2024
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.canlet.2006.09.019
dc.identifier.issn0304-3835
dc.identifier.pubmedidMEDLINE:17084965
dc.identifier.urihttps://doi.org/10.1016/j.canlet.2006.09.019
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79378
dc.identifier.wosidWOS:000246260100012
dc.information.autorucMedicina;Corvalan A;S/I;63885
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final106
dc.pagina.inicio100
dc.publisherELSEVIER IRELAND LTD
dc.revistaCANCER LETTERS
dc.rightsacceso restringido
dc.subjectmethylation
dc.subjecttumor suppressor genes
dc.subjectgallbladder carcinoma
dc.subjectCELL LUNG-CANCER
dc.subjectPROMOTER HYPERMETHYLATION
dc.subjectALLELOTYPING ANALYSIS
dc.subjectHOMOZYGOUS DELETIONS
dc.subjectISLAND METHYLATION
dc.subjectREVEALS MULTIPLE
dc.subjectBREAST-CANCER
dc.subjectALLELIC LOSS
dc.subjectFHIT GENE
dc.subject3P21.3
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFrequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma
dc.typeartículo
dc.volumen250
sipa.codpersvinculados63885
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
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