Regional Bias of Intratumoral Genetic Heterogeneity of Apoptosis-Related Genes BAX, APAF1, and FLASH in Colon Cancers with High Microsatellite Instability.
Dig Dis Sci
; 60(6): 1674-9, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25599959
ABSTRACT
BACKGROUND:
Apoptosis inactivation and intratumoral heterogeneity (ITH) are common features of cancers, including colorectal cancer (CRC). Inactivation of apoptosis prolongs cancer cell survival, and ITH may contribute to CRC progression.AIM:
To examine the presence and extent of mutational ITH in the pro-apoptotic genes APAF1, BAX, and FLASH and the association of mutational ITH with pathologic parameters of CRC.METHODS:
The ITH of mutations in the mononucleotide repeats of APAF1, BAX and FLASH in different tumors were analyzed in 16 cases of CRC with high microsatellite instability (MSI-H) and 41 cases of CRC with stable MSI/low MSI (MSS/MSI-L) by single-strand conformation polymorphism and DNA sequencing analyses.RESULTS:
Frameshift mutations of APAF1, BAX, and FLASH were identified in 19, 31, and 6 % of CRC with MSI-H, respectively, but also in cases of CRC with MSS/MSI-L. All but one CRC with a mutation (8/9) harbored regional ITH of the APAF1, BAX and FLASH frameshift mutations. ITH, however, was not associated with histopathologic features of CRC with MSI-H, suggesting that ITH might not be related to development of the MSI-H phenotype itself, but rather to disease progression.CONCLUSIONS:
Our results indicate that the APAF1, BAX, and FLASH genes not only harbor frameshift mutations but also demonstrate mutational ITH, which together might play a role in the tumorigenesis of CRC with MSI-H by affecting the apoptosis of cancer cells. Our data also suggest that multiregional mutation analysis is needed for a better evaluation of the mutation status in CRC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
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Mutação da Fase de Leitura
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Apoptose
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Neoplasias do Colo
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Heterogeneidade Genética
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Proteínas Reguladoras de Apoptose
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Proteína X Associada a bcl-2
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Fator Apoptótico 1 Ativador de Proteases
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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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
País/Região como assunto:
Asia
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2015
Tipo de documento:
Article