Allelic loss and promoter hypermethylation of the p(15INK4b) gene featuresin mouse radiation-induced lymphoid - but not myeloid - leukaemias

Mouse radiation-induced acute myeloid leukaemias (AMLs) which arose in a (C BA/H x C57BL/6) genetic background have a 45% incidence of loss of heterozy gosity (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 leuk aemogenesis. We addressed the question of p15(INK4b)/p16(INK4a)/p19(ARF) ge ne promoter hypermethylation in radiation-induced AMLs by comparison to TLs which arose in a similar (C57BL/6 x CBA/H) genetic background as a consequ ence of the same initiating dose of 3 Gy X-rays. Only one homozygous deleti on 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 promot er/exon 1 methylation was rare (<3%) in both. Thus, allelic loss and promot er hypermethylation of the p15(INK4b) gene is particular to radiation-induc ed lymphoid leukaemias and is independent of p16(INK4a) and p19(ARF) gene p romoter/exon 1 hypermethylation.