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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2013 Nov 29

PMID 24286026

Citations 76

Authors

Stuart Avery

Adam J Hirst

Duncan Baker

Chin Yan Lim

Sharmini Alagaratnam

Rolf I Skotheim

Ragnhild A Lothe

Martin F Pera

Alan Colman

Paul Robson

Peter W Andrews

Barbara B Knowles

Affiliations

Soon will be listed here.

Abstract

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.

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