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Role of telomeric sequences in murine radiation‐induced myeloid leukaemia
Author(s) -
Meijne E.I. M.,
Silver A.R. J.,
Bouffler S. D.,
Morris D. J.,
van Kampen E. Winter,
Spanjer S.,
Huiskamp R.,
Cox R.
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<230::aid-gcc2>3.0.co;2-z
Subject(s) - telomere , biology , germline , genotype , locus (genetics) , telomerase , genetics , somatic cell , germline mutation , microbiology and biotechnology , inbred strain , mutation , gene
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. Genes Chromosom Cancer 16:230–237 (1996) . © 1996 Wiley‐Liss, Inc.