KaryoTap Enables Aneuploidy Detection in Thousands of Single Human Cells

Mays, Joseph C.; Mei, Sally; Kogenaru, Manjunatha; Quysbertf, Helberth M.; Bosco, Nazario; Zhao, Xin; Bianchi, Joy J.; Goldberg, Aleah; Kidiyoor, Gururaj Rao; Holt, Liam J.; Fenyö, David; Davoli, Teresa

doi:10.1101/2023.09.08.555746

Cited by 2 publications

References 55 publications

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The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

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Chromosomal instability (CIN) is a hallmark of cancer and is associated with tumor cell malignancy. CIN triggers a chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes in chromosomes. CIN arises from errors in DNA replication and chromosome segregation during cell division, leading to the formation of cells with abnormal number and/or structure of chromosomes. Errors in DNA replication result from abnormal replication licensing as well as replication stress, such as double-strand breaks and stalled replication forks; meanwhile, errors in chromosome segregation stem from defects in chromosome segregation machinery, including centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, or defective sister chromatids cohesion. In normal cells, CIN is deleterious and is associated with DNA damage, proteotoxic stress, metabolic alteration, cell cycle arrest, and senescence. Paradoxically, despite these negative consequences, CIN is one of the hallmarks of cancer found in over 90% of solid tumors and in blood cancers. Furthermore, CIN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity, thereby facilitating adaptive resistance to therapies; however, excessive CIN could induce tumor cells death, leading to the “just-right” model for CIN in tumors. Elucidating the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor treatments. This review provides an overview of causes and consequences of CIN, as well as the paradox of CIN, a phenomenon that continues to perplex researchers. Finally, this review explores the potential of CIN-based anti-tumor therapy.

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The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

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KaryoTap Enables Aneuploidy Detection in Thousands of Single Human Cells

Mays,

Mei,

Kogenaru

et al. 2023

Preprint

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Investigating chromosomal instability and aneuploidy within tumors is essential for understanding their contribution to tumorigenesis and developing effective diagnostic and therapeutic strategies. Single-cell DNA sequencing (scDNA-seq) technologies have enabled such analyses, revealing aneuploidies specific to individual cells within the same tumor. However, scaling the throughput of these methods to identify aneuploidies occurring at low frequencies while maintaining high sensitivity has been difficult. To overcome this, we developed KaryoTap, a method combining custom targeted panels for the Tapestri scDNA-seq platform with a Gaussian mixture model analysis framework to enable detection of chromosome- and chromosome arm-scale aneuploidy in all human chromosomes across thousands of single cells simultaneously. This system will prove a powerful and flexible resource for the study of aneuploidy and chromosomal instability in tumors and normal tissues.

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KaryoTap Enables Aneuploidy Detection in Thousands of Single Human Cells

Cited by 2 publications

References 55 publications

The two sides of chromosomal instability: drivers and brakes in cancer

The two sides of chromosomal instability: drivers and brakes in cancer

KaryoTap Enables Aneuploidy Detection in Thousands of Single Human Cells

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