POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia

2015-01-13

"C:\Users\kurtw_000\Box Sync\DocDR\2014\02-08-2014d0943\POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia.pdf"

Abstract
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.

Some notes
-Spain paper
-Nature genetics paper
-q
	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.
-Chronic	lymphocytic	leukemia	(CLL)
-exome enrichment
-DNA sequencing
-alignment with CLUSTALX2
-retrovirus
-confocal microscopy
-ChIP assay
-TRF
-TRAP assay
-HTQFISH

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