High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity

0349651 - ÚEM 2011 RIV US eng J - Journal Article
Närvä, E. - Autio, R. - Rahkonen, N. - Kong, L. - Harrison, N. - Kitsberg, D. - Borghese, L. - Itskovitz-Eldor, J. - Rasool, O. - Dvořák, Petr - Hovatta, O. - Otonkoski, T. - Tuuri, T. - Cui, W. - Brüstle, O. - Baker, D. - Maltby, E. - Moore, H. D. - Benvenisty, N. - Andrews, P.W. - Yli-Harja, O. - Lehesmaa, R.
High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity.
Nature Biotechnology. Roč. 28, č. 4 (2010), s. 371-U103. ISSN 1087-0156. E-ISSN 1546-1696
Institutional research plan: CEZ:AV0Z50390512
Keywords : DNA * stem cell * cancer
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 31.085, year: 2010
http://arl-repository.lib.cas.cz/uloziste_av/UEM-P/cav_un_epca-0349651_01.pdf

Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected.
Permanent Link: http://hdl.handle.net/11104/0189830