TY - JOUR
T1 - Role of telomeric sequences in murine radiation-induced myeloid leukaemia
AU - Meijne, E. I.M.
AU - Silver, A. R.J.
AU - Bouffler, Simon
AU - Morris, D. J.
AU - Winter Van Kampen, E.
AU - Spanjer, S.
AU - Huiskamp, R.
AU - Cox, R.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1996/8
Y1 - 1996/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0029737498&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-2264(199608)16:4<230::AID-GCC2>3.0.CO;2-Z
DO - 10.1002/(SICI)1098-2264(199608)16:4<230::AID-GCC2>3.0.CO;2-Z
M3 - Article
C2 - 8875236
AN - SCOPUS:0029737498
SN - 1045-2257
VL - 16
SP - 230
EP - 237
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 4
ER -