Understanding How Genetic Mutations Collaborate with Genomic Instability in Cancer

Laura J Jilderda, Lin Zhou, Floris Foijer*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Chromosomal instability is the process of mis-segregation for ongoing chromosomes, which leads to cells with an abnormal number of chromosomes, also known as an aneuploid state. Induced aneuploidy is detrimental during development and in primary cells but aneuploidy is also a hallmark of cancer cells. It is therefore believed that premalignant cells need to overcome aneuploidy-imposed stresses to become tumorigenic. Over the past decade, some aneuploidy-tolerating pathways have been identified through small-scale screens, which suggest that aneuploidy tolerance pathways can potentially be therapeutically exploited. However, to better understand the processes that lead to aneuploidy tolerance in cancer cells, large-scale and unbiased genetic screens are needed, both in euploid and aneuploid cancer models. In this review, we describe some of the currently known aneuploidy-tolerating hits, how large-scale genome-wide screens can broaden our knowledge on aneuploidy specific cancer driver genes, and how we can exploit the outcomes of these screens to improve future cancer therapy.

Original languageEnglish
Article number342
Number of pages16
JournalCells
Volume10
Issue number2
DOIs
Publication statusPublished - 6-Feb-2021

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