Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma

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dc.catalogadorgjm
dc.contributor.authorWistuba Oyarzún, Ignacio
dc.contributor.authorAshfaq, Raheela
dc.contributor.authorMaitra, Anirban
dc.contributor.authorÁlvarez Pando, Héctor Andrés
dc.contributor.authorRiquelme Sánchez, Erick Marcelo
dc.contributor.authorGazdar, Adi F.
dc.date.accessioned2024-07-18T19:13:51Z
dc.date.available2024-07-18T19:13:51Z
dc.date.issued2002
dc.description.abstractThere is limited information about the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). Our recent allelotyping analyses have indicated that chromosome 3p loss of heterozygosity (LOH), including the fragile histidine triad (FHIT) candidate tumor-suppressor gene locus at 3p14.2, is frequently detected in this neoplasm. To investigate the role of the FHIT abnormalities in the multistage sequential development of GBC, 33 formalin-fixed paraffin-embedded invasive GBC specimens and 76 accompanying histologically normal (n = 43) and dysplastic (n = 33) epithelia were examined by nostaining for expression of Fhit protein. Allele loss at the FHIT gene locus (3p14.2) was studied in all GBCs and in a subset of accompanying gallbladder epithelia by polymerase chain reaction-based LOH analysis, using three 3p14.2 microsatellite markers. In addition, histologically normal epithelium from chronic cholecystitis (n = 19) and dysplasia (it = 13) from gallbladder specimens without cancer were examined for immunostaining and LOH. There was a progressive increase in both the frequency of loss of Fhit expression and LOH at FHIT with increasing severity of histopathological changes. FHIT abnormalities were occasionally demonstrated in histologically normal gallbladder epithelium. Dysplastic foci demonstrated frequent reduction or absence of Fhit immunostaining (38 to 55%) and FHIT allelic loss (33 to 46%). In invasive tumors, these abnormalities were even higher, with 79% reduction or absence of Fhit immunostaining and 76% FHIT allele loss. A high correlation (70%) was observed between Fhit immunostaining abnormalities and allele loss in GBC specimens (P < 0.05). Although a high frequency of FHIT locus breakpoints; were detected in both invasive and dysplastic gallbladder specimens, no intronic homozygous deletions on FHIT were detected in GBCs. FHIT gene abnormalities are nearly universal in GBC and these changes are detected early in the sequential development of this neoplasm. Our findings indicate that the FHIT gene is one of the chromosome 3p putative tumor suppressor genes involved in the pathogenesis of this highly malignant neoplasm.
dc.fuente.origenORCID
dc.identifier.doi10.1016/S0002-9440(10)61157-1
dc.identifier.issn0002-9440
dc.identifier.pubmedidMEDLINE:12057912
dc.identifier.urihttps://doi.org/10.1016/S0002-9440(10)61157-1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87125
dc.identifier.wosidWOS:000176056900019
dc.information.autorucEscuela de Medicina; Wistuba Oyarzún, Ignacio; S/I; 100278
dc.information.autorucEscuela de Medicina; Álvarez Pando, Héctor Andrés; S/I; 10806
dc.information.autorucEscuela de Medicina; Riquelme Sánchez, Erick Marcelo; 0000-0002-2696-7995; 1001194
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final2079
dc.pagina.inicio2073
dc.revistaThe American Journal of Pathology
dc.rightsacceso restringido
dc.subjectFHIT gene
dc.subjectChromosome 3P
dc.subjectLung cancer
dc.subjectAllele loss
dc.subjectPremalignant lesions
dc.subjectBronchial lesions
dc.subjectReveals multiple
dc.subjectBreast cancer
dc.subject5'-CPG ISLAND
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma
dc.typeartículo
dc.volumen160
sipa.codpersvinculados100278
sipa.codpersvinculados10806
sipa.codpersvinculados1001194
sipa.trazabilidadORCID;2024-07-15
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