title: Role of telomeric sequences in murine radiation-induced myeloid leukaemia.
abstract: A previous study indicated that a highly inbred CBA/H mouse colony contained four genotypic variants for telomere-like repeat (TLR) sequence arrays and that one variant subpopulation that constituted 20% of the colony contributed the vast majority (> 90%) of radiation-induced acute myeloid leukaemias (AMLs). Through screening of a satellite CBA/H colony and rescreening of the original colony, we show that, whereas germline telomere sequence polymorphism is frequent in CBA/H mice, there is no genetic link between a specific TLR locus variant and susceptibility to AML. Studies on telomere-hybridising fragments between 200 bp and 150 kb revealed that the germline telomere mutation frequency was highest for restriction fragments > 50 kb. The hypervariability of these high-molecular-weight fragments resulted in each CBA/H mouse from the highly inbred colony having a different genotype. Although it was not possible to ascribe a specific somatic telomere mutation to AML development, telomere rearrangements were common in induced AMLs. Some terminal telomere-hybridising restriction fragments were shortened in AML samples in comparison with normal tissue, but, insofar as the reduction in size was relatively small, it seems unlikely that telomere erosion is a major contributor to the molecular pathology of murine radiation-induced AML.
authors.affiliation: Netherlands Energy Research Foundation (ECN), Petten, The Netherlands.
authors.forename: E I
authors.initials: EI
authors.lastname: Meijne
authors.forename: A R
authors.initials: AR
authors.lastname: Silver
authors.forename: S D
authors.initials: SD
authors.lastname: Bouffler
authors.forename: D J
authors.initials: DJ
authors.lastname: Morris
authors.forename: E W
authors.initials: EW
authors.lastname: van Kampen
authors.forename: S
authors.initials: S
authors.lastname: Spanjer
authors.forename: R
authors.initials: R
authors.lastname: Huiskamp
authors.forename: R
authors.initials: R
authors.lastname: Cox
mesh_terms: D000818:Animals; D016521:Electrophoresis, Gel, Pulsed-Field; D007951:Leukemia, Myeloid / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D008808:Mice, Inbred CBA; D009693:Nucleic Acid Hybridization; D016615:Telomere / Q000235:genetics* / Q000528:radiation effects; D014965:X-Rays