Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis

Abstract

Ross Levine, Lambert Busque and colleagues report the identification of recurrent somatic mutations in TET2 in elderly female individuals with clonal hematopoiesis. The mutations were identified in individuals without clinically apparent hematological malignancies. Aging is characterized by clonal expansion of myeloid-biased hematopoietic stem cells and by increased risk of myeloid malignancies. Exome sequencing of three elderly females with clonal hematopoiesis, demonstrated by X-inactivation analysis, identified somatic TET2 mutations. Recurrence testing identified TET2 mutations in 10 out of 182 individuals with X-inactivation skewing. TET2 mutations were specific to individuals with clonal hematopoiesis without hematological malignancies and were associated with alterations in DNA methylation.