Gains of 20q11.21 in human pluripotent stem cells: Insights from cancer research

Nusa Krivec; Manjusha Ghosh; Claudia Spits

doi:10.1016/j.stemcr.2023.11.013

Gains of 20q11.21 in human pluripotent stem cells: Insights from cancer research

Nusa Krivec, Manjusha Ghosh, Claudia Spits

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Abstract

The genetic abnormalities observed in hPSC cultures worldwide have been suggested to pose an important hurdle in their safe use in regenerative medicine due to the possibility of oncogenic transformation by mutant cells in the patient posttransplantation. One of the best-characterized genetic lesions in hPSCs is the gain of 20q11.21, found in 20% of hPSC lines worldwide, and strikingly, also amplified in 20% of human cancers. In this review, we have curated the existing knowledge on the incidence of this mutation in hPSCs and cancer, explored the significance of chromosome 20q11.21 amplification in cancer progression, and reviewed the oncogenic role of the genes in the smallest common region of gain, to shed light on the significance of this mutation in hPSC-based cell therapy. Lastly, we discuss the state-of-the-art strategies devised to detect aneuploidies in hPSC cultures, avoid genetic changes in vitro cultures of hPSCs, and strategies to eliminate genetically abnormal cells from culture.

Original language	English
Pages (from-to)	11-27
Number of pages <span style="color:red"p> <font size="1.5"> ✽ </span> </font>	17
Journal	Stem Cell Reports
Volume	19
DOIs	https://doi.org/10.1016/j.stemcr.2023.11.013
Publication status	Published - 9 Jan 2024

Bibliographical note

Funding Information:
N.K. is a predoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen . M.S.G. is supported by the Methusalem funding to Karen Sermon by the Vrije Universiteit Brussel .

Funding Information:
N.K. is a predoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen. M.S.G. is supported by the Methusalem funding to Karen Sermon by the Vrije Universiteit Brussel. N.K. M.S.G. and C.S. contributed equally to conceptualizing and writing the manuscript. We, the authors and our immediate family members have no financial interests, positions, or related patents to declare. We are not members of the journal's advisory board.

Publisher Copyright:
© 2023 The Author(s)

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title = "Gains of 20q11.21 in human pluripotent stem cells: Insights from cancer research",

abstract = "The genetic abnormalities observed in hPSC cultures worldwide have been suggested to pose an important hurdle in their safe use in regenerative medicine due to the possibility of oncogenic transformation by mutant cells in the patient posttransplantation. One of the best-characterized genetic lesions in hPSCs is the gain of 20q11.21, found in 20% of hPSC lines worldwide, and strikingly, also amplified in 20% of human cancers. In this review, we have curated the existing knowledge on the incidence of this mutation in hPSCs and cancer, explored the significance of chromosome 20q11.21 amplification in cancer progression, and reviewed the oncogenic role of the genes in the smallest common region of gain, to shed light on the significance of this mutation in hPSC-based cell therapy. Lastly, we discuss the state-of-the-art strategies devised to detect aneuploidies in hPSC cultures, avoid genetic changes in vitro cultures of hPSCs, and strategies to eliminate genetically abnormal cells from culture.",

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Gains of 20q11.21 in human pluripotent stem cells: Insights from cancer research

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OZRMETH9: The Genetic Component to Infertility and Early Developmental Failure

FWOTM1016: The impact of recurrent chromosomal abnormalities on growth advantage and differentiation capacity of human pluripotent stem cells