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

被引:115
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
收藏
页码:379 / 386
页数:8
相关论文
共 36 条
  • [1] Generation of Sheffield (Shef) human embryonic stem cell lines using a microdrop culture system
    Aflatoonian, Behrouz
    Ruban, Ludmila
    Shamsuddin, Shamsul
    Baker, Duncan
    Andrews, Peter
    Moore, Harry
    [J]. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2010, 46 (3-4) : 236 - 241
  • [2] Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage
    Amps, Katherine
    Andrews, Peter W.
    Anyfantis, George
    Armstrong, Lyle
    Avery, Stuart
    Baharvand, Hossein
    Baker, Julie
    Baker, Duncan
    Munoz, Maria B.
    Beil, Stephen
    Benvenisty, Nissim
    Ben-Yosef, Dalit
    Biancotti, Juan-Carlos
    Bosman, Alexis
    Brena, Romulo Martin
    Brison, Daniel
    Caisander, Gunilla
    Camarasa, Maria V.
    Chen, Jieming
    Chiao, Eric
    Choi, Young Min
    Choo, Andre B. H.
    Collins, Daniel
    Colman, Alan
    Crook, Jeremy M.
    Daley, George Q.
    Dalton, Anne
    De Sousa, Paul A.
    Denning, Chris
    Downie, Janet
    Dvorak, Petr
    Montgomery, Karen D.
    Feki, Anis
    Ford, Angela
    Fox, Victoria
    Fraga, Ana M.
    Frumkin, Tzvia
    Ge, Lin
    Gokhale, Paul J.
    Golan-Lev, Tamar
    Gourabi, Hamid
    Gropp, Michal
    Lu Guangxiu
    Hampl, Ales
    Harron, Katie
    Healy, Lyn
    Herath, Wishva
    Holm, Frida
    Hovatta, Outi
    Hyllner, Johan
    [J]. NATURE BIOTECHNOLOGY, 2011, 29 (12) : 1132 - U113
  • [3] Amundson SA, 2000, CANCER RES, V60, P6101
  • [4] Overexpression of BCL2 enhances survival of human embryonic stem cells during stress and obviates the requirement for serum factors
    Ardehali, Reza
    Inlay, Matthew A.
    Ali, Shah R.
    Tang, Chad
    Drukker, Micha
    Weissman, Irving L.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (08) : 3282 - 3287
  • [5] Adaptation to culture of human embryonic stem cells and oncogenesis in vivo
    Baker, Duncan E. C.
    Harrison, Neil J.
    Maltby, Edna
    Smith, Kath
    Moore, Harry D.
    Shaw, Pamela J.
    Heath, Paul R.
    Holden, Hazel
    Andrews, Peter W.
    [J]. NATURE BIOTECHNOLOGY, 2007, 25 (02) : 207 - 215
  • [6] Self-renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase
    Becker, Klaus A.
    Ghule, Prachi N.
    Therrien, Jaclyn A.
    Lian, Jane B.
    Stein, Janet L.
    Van Wijnen, Andre J.
    Stein, Gary S.
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2006, 209 (03) : 883 - 893
  • [7] The landscape of somatic copy-number alteration across human cancers
    Beroukhim, Rameen
    Mermel, Craig H.
    Porter, Dale
    Wei, Guo
    Raychaudhuri, Soumya
    Donovan, Jerry
    Barretina, Jordi
    Boehm, Jesse S.
    Dobson, Jennifer
    Urashima, Mitsuyoshi
    Mc Henry, Kevin T.
    Pinchback, Reid M.
    Ligon, Azra H.
    Cho, Yoon-Jae
    Haery, Leila
    Greulich, Heidi
    Reich, Michael
    Winckler, Wendy
    Lawrence, Michael S.
    Weir, Barbara A.
    Tanaka, Kumiko E.
    Chiang, Derek Y.
    Bass, Adam J.
    Loo, Alice
    Hoffman, Carter
    Prensner, John
    Liefeld, Ted
    Gao, Qing
    Yecies, Derek
    Signoretti, Sabina
    Maher, Elizabeth
    Kaye, Frederic J.
    Sasaki, Hidefumi
    Tepper, Joel E.
    Fletcher, Jonathan A.
    Tabernero, Josep
    Baselga, Jose
    Tsao, Ming-Sound
    Demichelis, Francesca
    Rubin, Mark A.
    Janne, Pasi A.
    Daly, Mark J.
    Nucera, Carmelo
    Levine, Ross L.
    Ebert, Benjamin L.
    Gabriel, Stacey
    Rustgi, Anil K.
    Antonescu, Cristina R.
    Ladanyi, Marc
    Letai, Anthony
    [J]. NATURE, 2010, 463 (7283) : 899 - 905
  • [8] Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression
    Carvalho, B.
    Postma, C.
    Mongera, S.
    Hopmans, E.
    Diskin, S.
    van de Wiel, M. A.
    van Criekinge, W.
    Thas, O.
    Matthaei, A.
    Cuesta, M. A.
    Droste, J. S. Terhaar sive
    Craanen, M.
    Schroeck, E.
    Ylstra, B.
    Meijer, G. A.
    [J]. GUT, 2009, 58 (01) : 79 - 89
  • [9] Cowan CA, 2004, NEW ENGL J MED, V350, P1353, DOI 10.1056/NEJMsr040330
  • [10] The generation of six clinical-grade human embryonic stem cell lines
    Crook, Jeremy Micah
    Peura, Teija Tuulikki
    Kravets, Lucy
    Bosman, Alexis Gina
    Buzzard, Jeremy James
    Horne, Rachel
    Hentze, Hannes
    Dunn, Norris Ray
    Zweigerdt, Robert
    Chua, Florence
    Upshall, Alan
    Colman, Alan
    [J]. CELL STEM CELL, 2007, 1 (05) : 490 - 494