Impaired hydroxylation of 5-methylcytosine in myeloid cancers.pdfVIP

LETTER doi:10.1038/nature09586 Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 1 1 2 1,3 1 1 1 Myunggon Ko *{, Yun Huang *{, Anna M. Jankowska , Utz J. Pape , Mamta Tahiliani , Hozefa S. Bandukwala , Jungeun An {, 1 1 2 3 4 5 2 Edward D. Lamperti , Kian Peng Koh , Rebecca Ganetzky , X. Shirley Liu , L. Aravind , Suneet Agarwal , Jaroslaw P. Maciejewski 1 Anjana Rao { TET2 is a close relative of TET1, an enzyme that converts 5-methyl- and I1873T). HEK293T cells expressing Tet2 mutants P1287S, cytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA1,2. W1211R or C1834D (Supplementary Figs 2 and 3a) displayed low The gene encoding TET2 resides at chromosome 4q24, in a region 5hmC staining and strong 5mC staining (Supplementary Figs 3b, c showing recurrent microdeletions and copy-neutral loss of hetero- and 4c, d), indicating a role for these residues in the integrity of the zygosity (CN-LOH) in patients with diverse myeloid malignancies3. catalytic or DNA binding domains. Cells expressing Tet2(R1817S/M) Somatic TET2 mutations are frequently observed in myelodysplas- (Fig. 1a, Supplementary Figs 2 and 3a) were positive for 5hmC staining tic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/ but changes in 5mC staining could not be assessed reliably (Fig. 1b, c, MPN