Transition to homozygosity does not appear to provide a clonal advantage to hematopoietic progenitors carrying mutations in TET2.

摘要

TET2 mutations are frequently found in hematologic malignancies including myeloproliferative neoplasms (MPNs). We previously reported on the clonal evolution of TET2 mutations in 8 JAK2-V617F-positive MPN patients by genotyping single BFU-E colonies and found there is no strict temporal order of occurrence between the TET2 and JAK2 mutations.3 The majority of patients with MPN display heterozygous TET2 mutations, but cases with homozygous TET2 mutations due to loss of heterozygosity (LOH) have also been described. Our clonal analysis revealed that 4/8 patients had a very small proportion (l%-3%) of colonies that were homozygous for the TET2 mutation through a mechanism of uniparental disomy or deletion in the TET2 locus.