BCL-XL Mediates the Strong Selective Advantage of a 20q11.21 Amplification Commonly Found in Human Embryonic Stem Cell Cultures

被引：119

作者：

Avery, Stuart ^{[1
]}

Hirst, Adam J. ^{[1
,2
]}

Baker, Duncan ^{[3
]}

Lim, Chin Yan ^{[1
]}

Alagaratnam, Sharmini ^{[4
,5
]}

Skotheim, Rolf I. ^{[4
,5
]}

Lothe, Ragnhild A. ^{[4
,5
]}

Pera, Martin F. ^{[6
,7
,8
]}

Colman, Alan ^{[1
]}

Robson, Paul ^{[9
]}

Andrews, Peter W. ^{[2
]}

Knowles, Barbara B. ^{[1
]}

机构：

[1] ASTAR, Inst Med Biol, Singapore 138648, Singapore

[2] Univ Sheffield, Ctr Stem Cell Biol, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[3] Sheffield Childrens NHS Trust, Sheffield Diagnost Genet Serv, Sheffield S10 2TH, S Yorkshire, England

[4] Univ Oslo, Oslo Univ Hosp, Norwegian Radium Hosp, Dept Canc Prevent,Inst Canc Res, N-0310 Oslo, Norway

[5] Univ Oslo, Canc Stem Cell Innovat Ctr, N-0310 Oslo, Norway

[6] Univ Melbourne, Stem Cells Australia, Melbourne, Vic 3010, Australia

[7] Univ Melbourne, Florey Neurosci & Mental Hlth Inst, Melbourne, Vic 3010, Australia

[8] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia

[9] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore

来源：

STEM CELL REPORTS | 2013年 / 1卷 / 05期

基金：

英国医学研究理事会;

关键词：

COPY-NUMBER; HUMAN BLASTOCYSTS; CYCLE ENTRY; SELF-RENEWAL; LINES; CHROMOSOME; PROGRESSION; CANCER; DIFFERENTIATION; EXPRESSION;

D O I：

10.1016/j.stemcr.2013.10.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cells (hESCs) regularly acquire nonrandom genomic aberrations during culture, raising concerns about their safe therapeutic application. The International Stem Cell Initiative identified a copy number variant (CNV) amplification of chromosome 20q11.21 in 25% of hESC lines displaying a normal karyotype. By comparing four cell lines paired for the presence or absence of this CNV, we show that those containing this amplicon have higher population doubling rates, attributable to enhanced cell survival through resistance to apoptosis. Of the three genes encoded within the minimal amplicon and expressed in hESCs, only overexpression of BCL2L1 (BCL-XL isoform) provides control cells with growth characteristics similar to those of CNV-containing cells, whereas inhibition of BCL-XL suppresses the growth advantage of CNV cells, establishing BCL2L1 as a driver mutation. Amplification of the 20q11.21 region is also detectable in human embryonal carcinoma cell lines and some teratocarcinomas, linking this mutation with malignant transformation.

引用

页码：379 / 386

页数：8

共 36 条

[11] Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells [J].