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

J 2010

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

NARVA, Elisa, Reija AUTIO, Nelly RAHKONEN, Lingjia KONG, Neil HARRISON et. al.

Basic information

Original name

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

Authors

NARVA, Elisa (792 Turkey), Reija AUTIO (792 Turkey), Nelly RAHKONEN (246 Finland), Lingjia KONG (246 Finland), Neil HARRISON (826 United Kingdom of Great Britain and Northern Ireland), Danny KITSBERG (246 Finland), Lodovica BORGHESE (276 Germany), Joseph ITSKOVITZ-ELDOR (376 Israel), Omid RASOOL (376 Israel), Petr DVOŘÁK (203 Czech Republic, guarantor, belonging to the institution), Outi HOVATTA (246 Finland), Timo OTONSKI (246 Finland), Timo TUURI (246 Finland), Wei CUI (246 Finland), Oliver BRUSTLE (276 Germany), Duncan BAKER (276 Germany), Edna MALTBY (276 Germany), Harry D. MOORE (276 Germany), Nissim BEVENISTY (376 Israel), Peter W. ANDREWS (826 United Kingdom of Great Britain and Northern Ireland), Olli YLI-HARJA (792 Turkey) and Riita LAHESMAA (792 Turkey)

Edition

Nature Biotechnology, 2010, 1087-0156

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 31.090

RIV identification code

RIV/00216224:14110/10:00043710

Organization unit

Faculty of Medicine

UT WoS

000276462400026

Keywords in English

COMPARATIVE GENOMIC HYBRIDIZATION; ES CELLS; INSTABILITY; EXPRESSION; CANCER; CHROMOSOME-16; CARCINOMA; GENES

Změněno: 18/1/2011 14:52, prof. Ing. Petr Dvořák, CSc.

Abstract

V originále

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.

Links

LC06077, research and development project

Name: Centrum chemické genetiky

Investor: Ministry of Education, Youth and Sports of the CR

MSM0021622430, plan (intention)

Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies

Citovat

NARVA, Elisa, Reija AUTIO, Nelly RAHKONEN, Lingjia KONG, Neil HARRISON, Danny KITSBERG, Lodovica BORGHESE, Joseph ITSKOVITZ-ELDOR, Omid RASOOL, Petr DVOŘÁK, Outi HOVATTA, Timo OTONSKI, Timo TUURI, Wei CUI, Oliver BRUSTLE, Duncan BAKER, Edna MALTBY, Harry D. MOORE, Nissim BEVENISTY, Peter W. ANDREWS, Olli YLI-HARJA and Riita LAHESMAA. High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity. Nature Biotechnology. 2010, vol. 28, No 4, 7 pp. ISSN 1087-0156.

@article{879463,
   author = {Narva, Elisa and Autio, Reija and Rahkonen, Nelly and Kong, Lingjia and Harrison, Neil and Kitsberg, Danny and Borghese, Lodovica and ItskovitzandEldor, Joseph and Rasool, Omid and Dvořák, Petr and Hovatta, Outi and Otonski, Timo and Tuuri, Timo and Cui, Wei and Brustle, Oliver and Baker, Duncan and Maltby, Edna and Moore, Harry D. and Bevenisty, Nissim and Andrews, Peter W. and YliandHarja, Olli and Lahesmaa, Riita},
   article_number = {4},
   keywords = {COMPARATIVE GENOMIC HYBRIDIZATION; ES CELLS; INSTABILITY; EXPRESSION; CANCER; CHROMOSOME-16; CARCINOMA; GENES},
   language = {eng},
   issn = {1087-0156},
   journal = {Nature Biotechnology},
   title = {High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity},
   volume = {28},
   year = {2010}
}

TY  - JOUR
ID  - 879463
AU  - Narva, Elisa - Autio, Reija - Rahkonen, Nelly - Kong, Lingjia - Harrison, Neil - Kitsberg, Danny - Borghese, Lodovica - Itskovitz-Eldor, Joseph - Rasool, Omid - Dvořák, Petr - Hovatta, Outi - Otonski, Timo - Tuuri, Timo - Cui, Wei - Brustle, Oliver - Baker, Duncan - Maltby, Edna - Moore, Harry D. - Bevenisty, Nissim - Andrews, Peter W. - Yli-Harja, Olli - Lahesmaa, Riita
PY  - 2010
TI  - High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity
JF  - Nature Biotechnology
VL  - 28
IS  - 4
SN  - 10870156
KW  - COMPARATIVE GENOMIC HYBRIDIZATION
KW  - ES CELLS
KW  - INSTABILITY
KW  - EXPRESSION
KW  - CANCER
KW  - CHROMOSOME-16
KW  - CARCINOMA
KW  - GENES
N2  - 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.
ER  -

NARVA, Elisa, Reija AUTIO, Nelly RAHKONEN, Lingjia KONG, Neil HARRISON, Danny KITSBERG, Lodovica BORGHESE, Joseph ITSKOVITZ-ELDOR, Omid RASOOL, Petr DVOŘÁK, Outi HOVATTA, Timo OTONSKI, Timo TUURI, Wei CUI, Oliver BRUSTLE, Duncan BAKER, Edna MALTBY, Harry D. MOORE, Nissim BEVENISTY, Peter W. ANDREWS, Olli YLI-HARJA and Riita LAHESMAA. High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity. \textit{Nature Biotechnology}. 2010, vol.~28, No~4, 7 pp. ISSN~1087-0156.

Detailed Information on Publication Record