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Recurrent Somatic TET2 Mutations in Normal Elderly Individuals with Clonal Hematopoiesis

Overview
Journal Nat Genet
Specialty Genetics
Date 2012 Sep 25
PMID 23001125
Citations 426
Authors
Lambert Busque
Jay P Patel
Maria E Figueroa
Aparna Vasanthakumar
Sylvie Provost
Zineb Hamilou
Luigina Mollica
Juan Li
Agnes Viale
Adriana Heguy
Maryam Hassimi
Nicholas Socci
Parva K Bhatt
Mithat Gonen
Christopher E Mason
Ari Melnick
Lucy A Godley
Cameron W Brennan
Omar Abdel-Wahab
Ross L Levine
Affiliations
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Abstract

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.

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