Specificity of loss of heterozygosity in radiation-induced mouse myeloid and lymphoid leukaemias.
OBJECTIVE
To determine whether loss of heterozygosity (LOH) at specific chromosomal loci in radiation-induced leukaemias, arising in a similar genetic background, is leukaemia-type specific (myeloid versus lymphoid) or common to both.


METHODS
Leukaemias that arose in 3 Gy X-irradiated (CBA/H x C57BL/6)F1 intercross and backcross mice were diagnosed as acute myeloid leukaemia (AML) or thymic lymphoma (TL). LOH was determined using 28 polymorphic microsatellite markers distributed over seven chromosomes using control and leukaemic DNA from individual mice.


RESULTS
LOH incidences of 0-20% were observed at most loci in both leukaemia types. Specific LOH incidences of 38-76% were observed for myeloid (chromosome 2) and lymphoid (chromosomes 11 and 14) leukaemias. Chromosome 4 LOH was frequently (38-50%) observed in both types, although the commonly deleted regions differed. LOH was detected at either chromosome 2 or 4 in AML and either chromosome 4 or 11 in TL.


CONCLUSIONS
LOH incidences of 38-76% suggest a causal role of particular loci which is mainly, but not exclusively, dependent on leukaemia type. LOH incidences of 0-20% at other loci in both leukaemias suggest that many genetic deletions are non-causal and incidental in radiation-leukaemogenesis.
Cleary
H J
HJ
MRC Radiation and Genome Stability Unit, Harwell, Didcot, Oxfordshire, UK.
Wright
E
E
Plumb
M
M
D000818:Animals; D002875:Chromosomes / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000209:etiology / Q000235:genetics*; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018895:Microsatellite Repeats