Evidence for clustered tumour suppressor gene loci on mouse chromosomes 2 and 4 in radiation-induced acute myeloid leukaemia.
Int J Radiat Biol
; 82(6): 383-91, 2006 Jun.
Article
en En
| MEDLINE
| ID: mdl-16846973
ABSTRACT
PURPOSE:
To investigate the influence of genetic and epigenetic factors on allelic loss on chromosomes 2 and 4 in mouse radiation-induced acute myeloid leukaemia (r-AML).METHODS:
r-AML that arose in (CBA/HxC57BL/6)F1xCBA/H and F1xC57BL/6 mice were screened for transcription factor PU1 (also known as SPI-1) gene mutations and methylation of the paired box gene 5 (Pax5) gene promoter. We have increased the statistical significance of a genetic linkage analysis of affected F1xCBA/H mice to test for linkage to loci implicated directly or indirectly with r-AML-susceptibility.RESULTS:
There was a statistically significant difference ( p < 10-4) in the frequency of PU1 gene mutations in F1xCBA/H and F1xC57BL/6 r-AML, implicating a second linked but genotype-dependent myeloid leukaemia suppressor gene on chromosome 2. A suggestive CBA/H r-AML-resistance locus maps within 10 cM of the minimally deleted region on chromosome 4. The Pax5 gene promoter is subject to ongoing subclonal promoter methylation in the r-AML, evidence that Pax5 gene silencing confers a selective advantage during clonal expansion in vivo.CONCLUSIONS:
Allelic loss in mouse r-AML and subsequent tumour suppressor gene mutation (PU1) or silencing (Pax5) is strongly influenced by genetic background and/or epigenetic factors, and driven by in vivo clonal selection.
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Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Leucemia Inducida por Radiación
/
Genes Supresores de Tumor
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
Int J Radiat Biol
Asunto de la revista:
RADIOLOGIA
Año:
2006
Tipo del documento:
Article