Loss of heterozygosity in spontaneous and X-ray-induced intestinal tumors arising in F1 hybrid min mice: evidence for sequential loss of APC(+) and Dpc4 in tumor development.
Genes Chromosomes Cancer
; 28(4): 387-94, 2000 Aug.
Article
en En
| MEDLINE
| ID: mdl-10862047
ABSTRACT
Min (multiple intestinal neoplasia) mice carry a mutant allele of the murine Apc (adenomatous polyposis coli) locus and are predisposed to intestinal adenoma formation in the intestinal tract. Early studies have shown complete loss of function of Apc by whole chromosome loss on the tumor-sensitive C57BL/6J genetic background and in AKR x B6 F1 hybrids. Gamma-radiation-induced chromosomal losses focus the critical region on wt Apc, but because of the limited number of polymorphic markers used, no other critical regions of loss on chromosome 18 were identified. Using intestinal tumors arising spontaneously and induced by X-rays in CBA/H x C57BL/6J F1 hybrid mice and high-resolution microsatellite loss of heterozygosity (LOH) techniques, we provide mapping data for wt Apc loss, which confirms and extends earlier observations. In addition, high-frequency loss events at the Dpc4 locus were found in both spontaneous and radiation-induced tumors. These data identified LOH of Dpc4 as a critical secondary event following complete functional loss of Apc. LOH across the Trp53 genomic region of chromosome 11 was not observed. No LOH was recorded for the Mom1 candidate gene Pla2g2a or for 9 out of 10 polymorphic markers from the Mom1 genomic region on murine chromosome 4. One marker mapping distal to Pla2g2a showed LOH in a small minority of spontaneous tumors. These data support the contention that Mom1 does not act as a classical tumor suppressor. Overall, our data indicates a significant role for Dpc4 mutation in intestinal tumor progression in the mouse and provides further evidence for the importance of interstitial chromosome losses in radiation tumorigenesis.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Genes APC
/
Pérdida de Heterocigocidad
/
Proteínas de Unión al ADN
/
Neoplasias Intestinales
/
Neoplasias Inducidas por Radiación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Genes Chromosomes Cancer
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2000
Tipo del documento:
Article
País de afiliación:
Reino Unido