Comprehensive mutation analysis in colorectal flat adenomas.
PLoS One
; 7(7): e41963, 2012.
Article
em En
| MEDLINE
| ID: mdl-22848674
ABSTRACT
BACKGROUND:
Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes.METHODS:
A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in "hot spot" regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (ß-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing.RESULTS:
APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, pâ=â0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes.CONCLUSION:
The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Análise Mutacional de DNA
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Neoplasias Colorretais
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Adenoma
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Biologia Computacional
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
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda