Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas

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dc.contributor.authorWistuba, II
dc.contributor.authorMiquel, JF
dc.contributor.authorGazdar, AF
dc.contributor.authorAlbores-Saavedra, J
dc.date.accessioned2025-01-21T01:32:21Z
dc.date.available2025-01-21T01:32:21Z
dc.date.issued1999
dc.description.abstractAlthough most gallbladder carcinomas evolve from dysplasia and carcinoma in situ, the role of gallbladder adenomas in the pathogenesis of gallbladder carcinoma is still controversial. A series of molecular changes including loss of heterozygosity (LOH) at 17p (TP53 gene), 13q (RB gene), 18q (DCC gene), and 9p21 (CDKN2a gene) chromosomal regions have been identified in dysplasias, carcinomas in situ, and invasive carcinomas of the gallbladder, whereas mutations in K- and N-ras genes are rare. To determine whether the molecular abnormalities of adenomas are similar to those found in carcinomas, we obtained extracted DNA from precisely microdissected tissue from 16 gallbladder adenomas (14 pyloric and 2 intestinal-type). We determined the presence of mutations in TP53, K- and N-ras genes, and LOH at five chromosomal regions (5q22 APC-MCC region, RE, TP53, DCC and 9p21-CDKN2 alpha). For the TP53 mutation study, single strand conformational polymorphism (SSCP) analysis in exons 4 to 8 were performed. K- and N-ras mutations detection was performed by designed restriction fragment length polymorphism (RFLP) method and sequencing. Only a single LOH (at 5q22) was detected in a gallbladder adenoma of intestinal type. No mutations at the TP53 were detected. Four adenomas (25%) showed K-ras mutations (two in codon 12 and two in codon 61). We conclude that gallbladder adenoma lacks the molecular changes frequently detected in dysplasia, carcinoma in situ, and invasive carcinoma of the gallbladder. Likewise the occurrence of K-ras mutations at codon 12 and 61 in 25% of adenomas strongly suggests that these lesions are not precursors of invasive gallbladder carcinoma. HUM PATHOL 30:21-25. Copyright (C) 1999 by W.B. Saunders Company.
dc.fuente.origenWOS
dc.identifier.issn0046-8177
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/97245
dc.identifier.wosidWOS:000078101800004
dc.issue.numero1
dc.language.isoen
dc.pagina.final25
dc.pagina.inicio21
dc.revistaHuman pathology
dc.rightsacceso restringido
dc.subjectgallbladder adenomas
dc.subjectgallbladder carcinoma pathogenesis
dc.subjectTP53 gene mutations
dc.subjectras gene mutations
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas
dc.typeartículo
dc.volumen30
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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