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Genes Chromosomes Cancer. 1996 Aug;16(4):230-7.

Role of telomeric sequences in murine radiation-induced myeloid leukaemia.

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1
Netherlands Energy Research Foundation (ECN), Petten, The Netherlands.

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.

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