High Prevalence of Acquired Cancer-related Mutations in 146 Human Pluripotent Stem Cell Lines and Their Differentiated Derivatives

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2024 Jan 10

PMID 38195986

Authors

Elyad Lezmi

Jonathan Jung

Nissim Benvenisty

Affiliations

Soon will be listed here.

Abstract

To survey cancer-related mutations in human pluripotent stem cells and their derivatives, we analyzed >2,200 transcriptomes from 146 independent lines in the NCBI's Sequence Read Archive. Twenty-two per cent of samples had at least one cancer-related mutation; of these, 64% had TP53 mutations, which conferred a pronounced selective advantage, perturbed target gene expression and altered cellular differentiation. These findings underscore the need for robust surveillance of cancer-related mutations in pluripotent cells, especially in clinical applications.

Citing Articles

A framework for neural organoids, assembloids and transplantation studies.

Pasca S, Arlotta P, Bateup H, Camp J, Cappello S, Gage F Nature. 2024; 639(8054):315-320.

PMID: 39653126 DOI: 10.1038/s41586-024-08487-6.

Using magnetic resonance relaxometry to evaluate the safety and quality of induced pluripotent stem cell-derived spinal cord progenitor cells.

Tan J, Chen J, Roxby D, Chooi W, Nguyen T, Ng S Stem Cell Res Ther. 2024; 15(1):465.

PMID: 39639398 PMC: 11622678. DOI: 10.1186/s13287-024-04070-y.

Longitudinal analysis of genetic and epigenetic changes in human pluripotent stem cells in the landscape of culture-induced abnormality.

Kim Y, Kang B, Kweon S, Oh S, Kim D, Gil D Exp Mol Med. 2024; 56(11):2409-2422.

PMID: 39482531 PMC: 11612254. DOI: 10.1038/s12276-024-01334-8.

De Novo Cancer Mutations Frequently Associate with Recurrent Chromosomal Abnormalities during Long-Term Human Pluripotent Stem Cell Culture.

Al Delbany D, Ghosh M, Krivec N, Huyghebaert A, Regin M, Duong M Cells. 2024; 13(16).

PMID: 39195283 PMC: 11353044. DOI: 10.3390/cells13161395.

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Stavish D, Price C, Gelezauskaite G, Alsehli H, Leonhard K, Taapken S Stem Cell Reports. 2024; 19(8):1217-1232.

PMID: 38964325 PMC: 11368687. DOI: 10.1016/j.stemcr.2024.06.003.

References

Baker D, Harrison N, Maltby E, Smith K, Moore H, Shaw P . Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol. 2007; 25(2):207-15. DOI: 10.1038/nbt1285. View

Halliwell J, Barbaric I, Andrews P . Acquired genetic changes in human pluripotent stem cells: origins and consequences. Nat Rev Mol Cell Biol. 2020; 21(12):715-728. DOI: 10.1038/s41580-020-00292-z. View

Andrews P, Barbaric I, Benvenisty N, Draper J, Ludwig T, Merkle F . The consequences of recurrent genetic and epigenetic variants in human pluripotent stem cells. Cell Stem Cell. 2022; 29(12):1624-1636. DOI: 10.1016/j.stem.2022.11.006. View

Mayshar Y, Ben-David U, Lavon N, Biancotti J, Yakir B, Clark A . Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell. 2010; 7(4):521-31. DOI: 10.1016/j.stem.2010.07.017. View

Lezmi E, Benvenisty N . The Tumorigenic Potential of Human Pluripotent Stem Cells. Stem Cells Transl Med. 2022; 11(8):791-796. PMC: 9397652. DOI: 10.1093/stcltm/szac039. View

Merkle F, Ghosh S, Kamitaki N, Mitchell J, Avior Y, Mello C . Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature. 2017; 545(7653):229-233. PMC: 5427175. DOI: 10.1038/nature22312. View

Avior Y, Lezmi E, Eggan K, Benvenisty N . Cancer-Related Mutations Identified in Primed Human Pluripotent Stem Cells. Cell Stem Cell. 2020; 28(1):10-11. DOI: 10.1016/j.stem.2020.11.013. View

Rouhani F, Zou X, Danecek P, Badja C, Amarante T, Koh G . Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells. Nat Genet. 2022; 54(9):1406-1416. PMC: 9470532. DOI: 10.1038/s41588-022-01147-3. View

Gore A, Li Z, Fung H, Young J, Agarwal S, Antosiewicz-Bourget J . Somatic coding mutations in human induced pluripotent stem cells. Nature. 2011; 471(7336):63-7. PMC: 3074107. DOI: 10.1038/nature09805. View

10.

Tate J, Bamford S, Jubb H, Sondka Z, Beare D, Bindal N . COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2018; 47(D1):D941-D947. PMC: 6323903. DOI: 10.1093/nar/gky1015. View

11.

Lezmi E, Benvenisty N . Identification of cancer-related mutations in human pluripotent stem cells using RNA-seq analysis. Nat Protoc. 2021; 16(9):4522-4537. DOI: 10.1038/s41596-021-00591-5. View

12.

Kosanke M, Osetek K, Haase A, Wiehlmann L, Davenport C, Schwarzer A . Reprogramming enriches for somatic cell clones with small-scale mutations in cancer-associated genes. Mol Ther. 2021; 29(8):2535-2553. PMC: 8353200. DOI: 10.1016/j.ymthe.2021.04.007. View

13.

Willis A, Jung E, Wakefield T, Chen X . Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes. Oncogene. 2004; 23(13):2330-8. DOI: 10.1038/sj.onc.1207396. View

14.

Menendez D, Inga A, Resnick M . The expanding universe of p53 targets. Nat Rev Cancer. 2009; 9(10):724-37. DOI: 10.1038/nrc2730. View

15.

Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M . KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 1998; 27(1):29-34. PMC: 148090. DOI: 10.1093/nar/27.1.29. View

16.

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

17.

Luo W, Brouwer C . Pathview: an R/Bioconductor package for pathway-based data integration and visualization. Bioinformatics. 2013; 29(14):1830-1. PMC: 3702256. DOI: 10.1093/bioinformatics/btt285. View