Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells.

ABSTRACT: TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2^-/- mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2^-/- tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2^-/- Lin^-c-Kit⁺ cells shows higher mutation frequencies in Tet2^-/- cells. We further show that t

SUBMITTER: Pan F 

PROVIDER: S-EPMC5414116 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature