title: Microsatellite analysis of recurrent chromosome 2 deletions in acute myeloid leukaemia induced by radiation in F1 hybrid mice.
abstract: Deletions and/or rearrangements involving one copy of chromosome 2 are consistent and early events in the development of murine acute myeloid leukaemia (AML) by radiation. More than 90% of AMLs induced in the CBA strain of mice express such cytogenetic alterations, with chromosome 2 breakpoints clustering in the C and F regions of the chromosome. In inbred mouse strains, the molecular resolution of these breakpoints is problematic. However, by using x-ray-induced AMLs in FI progeny of genetically divergent CBA/H x C57BI, it has been possible to show region-specific loss of heterozygosity (LOH) in genetically linked sets of chromosome 2 microsatellite alleles from one of the two parental chromosomes. In the majority of cases, an acceptable concordance was shown for AML chromosome 2 deletion, as defined by microsatellites and as revealed by G-band cytogenetics. A degree of breakpoint clustering was found, but the identification of a number of deletion types, based on the position of proximal and distal breakpoints as defined by microsatellite analysis, strongly supports a leukaemogenic mechanism involving gene deletion. No bias towards loss of CBA or C57BI alleles was observed, and the gender of AML-presenting animals did not appear to influence the parental origin of the deletions. A molecular map of chromosome 2 breakpoints has now been established in FI AMLs as a first step towards the molecular cloning of breakpoint sequences.
authors.affiliation: National Radiological Protection Board, Didcot, Oxon, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Clark
authors.forename: E I
authors.initials: EI
authors.lastname: Meijne
authors.forename: S D
authors.initials: SD
authors.lastname: Bouffler
authors.forename: R
authors.initials: R
authors.lastname: Huiskamp
authors.forename: C J
authors.initials: CJ
authors.lastname: Skidmore
authors.forename: R
authors.initials: R
authors.lastname: Cox
authors.forename: A R
authors.initials: AR
authors.lastname: Silver
mesh_terms: D000208:Acute Disease; D000818:Animals; D002678:Chimera; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000528:radiation effects*; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D014965:X-Rays