POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-05

AUTHORS

Andrew J Ramsay, Víctor Quesada, Miguel Foronda, Laura Conde, Alejandra Martínez-Trillos, Neus Villamor, David Rodríguez, Agnieszka Kwarciak, Cecilia Garabaya, Mercedes Gallardo, Mónica López-Guerra, Armando López-Guillermo, Xose S Puente, María A Blasco, Elías Campo, Carlos López-Otín

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. 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. More... »

PAGES

526

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.2584

DOI

http://dx.doi.org/10.1038/ng.2584

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012561030

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23502782


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