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Microsatellite analysis of recurrent chromosome 2 deletions in acute myeloid leukaemia induced by radiation in FI hybrid mice
Author(s) -
Clark D. J.,
Meijne E.I. M.,
Bouffler S. D.,
Huiskamp R.,
Skidmore C. J.,
Cox R.,
Silver A.R. J.
Publication year - 1996
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199608)16:4<238::aid-gcc3>3.0.co;2-z
Subject(s) - breakpoint , biology , genetics , loss of heterozygosity , microsatellite , chromosome , cytogenetics , microbiology and biotechnology , allele , gene
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 × 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. Genes Chromosom Cancer 16:238–246 (1996) . © 1996 Wiley‐Liss, Inc.