Allelic loss and promoter hypermethylation of the p15INK4b gene features in mouse radiation-induced lymphoid - but not myeloid - leukaemias.
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 p15INK4b and p16INK4a alleles, so this may be common to mouse radiation myeloid and lymphoid leukaemogenesis. We addressed the question of p15INK4b/p16INK4a/p19ARF 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 approximately 100 leukaemias analysed. p15INK4b gene promoter/exon 1 hypermethylation was readily detected (21%) in the lymphoid but not myeloid (3.1%) leukaemias, and p16INK4a and p19ARF gene promoter/exon 1 methylation was rare (<3%) in both. Thus, allelic loss and promoter hypermethylation of the p15INK4b gene is particular to radiation-induced lymphoid leukaemias and is independent of p16INK4a and p19ARF gene promoter/exon 1 hypermethylation.
Cleary
H J
HJ
MRC Radiation and Genome Stability Unit, Chilton, Didcot, Oxford OX11 0RD, UK.
Boulton
E
E
Plumb
M
M
D000483:Alleles; D000818:Animals; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019175:DNA Methylation; D019942:Genes, p16; D007945:Leukemia, Lymphoid / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008868:Microtubule Proteins; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D050777:Stathmin; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D008868:Microtubule Proteins; D010750:Phosphoproteins; D050777:Stathmin; C493994:Stmn1 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins