Mutation in TET2 in Myeloid Cancers

TLDR: Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers and were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that were analyzed.

Abstract: Background The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined. We initially identified deletions or mutations in TET2 in three patients with myelo- dysplastic syndromes, in three of five patients with myeloproliferative disorders, in two patients with primary AML, and in one patient with secondary AML. We selected the six patients with myelodysplastic syndromes or AML because they carried acquired rearrangements on chromosome 4q24; we selected the five patients with myelopro- liferative disorders because they carried a dominant clone in hematopoietic progeni- tor cells that was positive for the V617F mutation in the Janus kinase 2 (JAK2) gene. TET2 defects were observed in 15 of 81 patients with myelodysplastic syndromes (19%), in 24 of 198 patients with myeloproliferative disorders (12%) (with or with- out the JAK2 V617F mutation), in 5 of 21 patients with secondary AML (24%), and in 2 of 9 patients with chronic myelomonocytic leukemia (22%). TET2 defects were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that we analyzed. Conclusions Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers.