Allelic loss and promoter hypermethylation of the p15INK4b gene features in mouse radiation-induced lymphoid -: but not myeloid -: leukaemias

被引:21
作者
Cleary, HJ [1 ]
Boulton, E [1 ]
Plumb, M [1 ]
机构
[1] MRC, Radiat & Genome Stabil Unit, Didcot OX11 0RD, Oxon, England
基金
英国医学研究理事会;
关键词
radiation; leukaemia; p15(INK4b);
D O I
10.1038/sj.leu.2401616
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mouse radiation-induced acute myeloid leukaemias (AMLs) which arose in a (CBA/H x C57BL/6) genetic background have a 45% incidence of loss of heterozygosity (LOH) on chromosome 4. Frequent chromosome 4 LOH in mouse radiation-induced (C57BL/6 x RF/J) thymic lymphomas (TLs) is associated with promoter/exon 1 region hypermethylation of the remaining p15(INK4b) and p16(INK4a) alleles, so this may be common to mouse radiation myeloid and lymphoid leukaemogenesis. We addressed the question of p15(INK4b)/p16(INK4a)/p19(ARF) gene promoter hypermethylation in radiation-induced AMLs by comparison to TLs which arose in a similar (C57BL/6 x CBA/H) genetic background as a consequence of the same initiating dose of 3 Gy X-rays. Only one homozygous deletion was detected in the similar to 100 leukaemias analysed. p15(INK4b) gene promoter/exon 1 hypermethylation was readily detected (21%) in the lymphoid but not myeloid (3.1%) leukaemias, and p16(INK4a) and p19(ARF) gene promoter/exon 1 methylation was rare (<3%) in both. Thus, allelic loss and promoter hypermethylation of the p15(INK4b) gene is particular to radiation-induced lymphoid leukaemias and is independent of p16(INK4a) and p19(ARF) gene promoter/exon 1 hypermethylation.
引用
收藏
页码:2049 / 2052
页数:4
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