High frequency of copy-neutral LOH in MUTYH-associated polyposis carcinomas.
J Pathol
; 216(1): 25-31, 2008 Sep.
Article
en En
| MEDLINE
| ID: mdl-18506705
ABSTRACT
Genetic instability is known to drive colorectal carcinogenesis. Generally, a distinction is made between two types of genetic instability chromosomal instability (CIN) and microsatellite instability (MIN or MSI). Most CIN tumours are aneuploid, whereas MSI tumours are considered near-diploid. However, for MUTYH-associated polyposis (MAP) the genetic instability involved in the carcinogenesis remains unclear, as near-diploid adenomas, aneuploid adenomas and near-diploid carcinomas have been reported. Remarkably, our analysis of 26 MAP carcinomas, using SNP arrays and flow sorting, showed that these tumours are often near-diploid (52%) and mainly contain chromosomal regions of copy-neutral loss of heterozygosity (LOH) (71%). This is in contrast to sporadic colon cancer, where physical loss is the main characteristic. The percentage of chromosomal gains (24%) is comparable to sporadic colorectal cancers with CIN. Furthermore, we verified our scoring of copy-neutral LOH versus physical loss in MAP carcinomas by two methods:
fluorescence in situ hybridization, and LOH analysis using polymorphic markers on carcinoma fractions purified by flow sorting. The results presented in this study suggest that copy-neutral LOH is an important mechanism in the tumorigenesis of MAP.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poliposis Adenomatosa del Colon
/
Pérdida de Heterocigocidad
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Inestabilidad Cromosómica
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ADN Glicosilasas
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Aged
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Humans
/
Middle aged
Idioma:
En
Revista:
J Pathol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Países Bajos