Mutational analyses of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability.
Jpn J Cancer Res
; 89(12): 1284-91, 1998 Dec.
Article
em En
| MEDLINE
| ID: mdl-10081489
ABSTRACT
It has been recognized that gastric cancer often shows histological heterogeneity in a single tumor. Although microsatellite instability (MSI) has been reported in gastric cancer, the significance of genomic instability in gastric cancers with histological heterogeneity within a single tumor has never been addressed. We investigated MSI at 8 microsatellite loci in 40 normal/tumor DNA pairs from 20 gastric cancers with histological heterogeneity. Six of 20 patients (10 DNAs of 40 tumor DNAs) had severe MSI in more than 3 loci. Four of the MSI-positive cases had frameshift mutations in the poly(A)10 tract of the TGF beta RII gene. This mutation was found only in the MSI-positive component in the 2 cases (cases 4 and 5) in which only 1 component exhibited MSI. The other 4 cases demonstrated homozygous or heteroclonal mutations (1 and 2 base deletions) in the poly(A)8 tract of the hMSH3 gene; no mutation was detected in the poly(C)8 tract of the hMSH6 gene in any of the MSI-positive cases. The profile of alterations in multiple targets was different between the 2 components in most of the cases (5/6). These findings suggest that mismatch repair deficiency in MSI-positive tumors causes multiple gene inactivations through frameshift mutations in short repetitive sequences in a heterogeneous way within a histologically heterogeneous tumor.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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DNA de Neoplasias
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Proteínas Fúngicas
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Carcinoma
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Receptores de Fatores de Crescimento Transformadores beta
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Repetições de Microssatélites
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Proteínas de Saccharomyces cerevisiae
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Proteínas de Ligação a DNA
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Proteínas de Neoplasias
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Jpn J Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
1998
Tipo de documento:
Article