viernes, 22 de marzo de 2013

POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia : Nature Genetics : Nature Publishing Group

POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia : Nature Genetics : Nature Publishing Group



POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia




Nature Genetics
(2013)
doi:10.1038/ng.2584


Received


Accepted


Published online



Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults1, 2, 3. We have analyzed exome sequencing data from 127 individuals with CLL and Sanger sequencing data from 214 additional affected individuals, identifying recurrent somatic mutations in POT1 (encoding protection of telomeres 1) in 3.5% of the cases, with the frequency reaching 9% when only individuals without IGHV@ mutations were considered. POT1 encodes a component of the shelterin complex and is the first member of this telomeric structure found to be mutated in human cancer. Somatic mutation of POT1 primarily occurs in gene regions encoding the two oligonucleotide-/oligosaccharide-binding (OB) folds and affects key residues required to bind telomeric DNA. POT1-mutated CLL cells have numerous telomeric and chromosomal abnormalities that suggest that POT1 mutations favor the acquisition of the malignant features of CLL cells. The identification of POT1 as a new frequently mutated gene in CLL may facilitate novel approaches for the clinical management of this disease.


At a glance



Figures





left


  1. Structural impact of POT1 somatic mutations.
    Figure 1

  2. Biological properties of wild-type POT1 and the Tyr36Asn and Tyr223Cys POT1 mutants.
    Figure 2

  3. Chromosomal aberrations in cells from individuals with CLL expressing mutated POT1.
    Figure 3



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