Effect of mutation order on myeloproliferative neoplasms.

ABSTRACT:

Background

Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired.

Methods

We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells.

Results

The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was a

SUBMITTER: Ortmann CA 

PROVIDER: S-EPMC4660033 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature