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<p>Abstract</p> <p>Background</p> <p>The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, <it>RASSF10 </it>is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of <it>RASSF10 </it>in normal human bone marrow. We also determined the methylation status of CpG islands associated with <it>RASSF1–10 </it>in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples.</p> <p>Results</p> <p>COBRA and bisulphite sequencing revealed <it>RASSF6 </it>and <it>RASSF10 </it>were the only RASSF members with a high frequency of leukaemia-specific methylation. <it>RASSF6 </it>was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst <it>RASSF10 </it>was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. <it>RASSF6 </it>and <it>RASSF10 </it>expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC).</p> <p>Conclusion</p> <p>This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of <it>RASSF6 </it>or <it>RASSF10 </it>in cancer. These data show epigenetic inactivation of the candidate TSGs <it>RASSF6 </it>and <it>RASSF10 </it>is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member <it>RASSF10 </it>and its potential role in leukaemia.</p>