Dissecting Intra-Tumor Heterogeneity by the Analysis of Copy Number Variations in Single Cells: The Neuroblastoma Case Study

Autor: Valeria D'Argenio, Varun Shankar, Rossella Tomaiuolo, Marcella Nunziato, Francesca Borrillo, Federica Cariati
Přispěvatelé: Cariati, Federica, Borrillo, Francesca, Shankar, Varun, Nunziato, Marcella, D'Argenio, Valeria, Tomaiuolo, Rossella
Jazyk: angličtina
Rok vydání: 2019
Předmět:
single cell isolation
DNA Copy Number Variations
Cell
chromosomal pattern
Computational biology
Biology
Catalysis
DNA sequencing
Catalysi
Inorganic Chemistry
lcsh:Chemistry
Genetic Heterogeneity
Neuroblastoma
Cell Line
Tumor
Genotype
Technical Note
medicine
Humans
Copy-number variation
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Chromosome Aberrations
Whole Genome Sequencing
whole genome amplification
Organic Chemistry
copy number variation
Computational Biology
Cancer
intra-tumor heterogeneity
Computer Science Applications1707 Computer Vision and Pattern Recognition
General Medicine
medicine.disease
Computer Science Applications
medicine.anatomical_structure
copy number variations
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
next-generation sequencing
Single-Cell Analysis
Immortalised cell line
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 4, p 893 (2019)
International Journal of Molecular Sciences
ISSN: 1422-0067
Popis: Tumors often show intra-tumor heterogeneity because of genotypic differences between all the cells that compose it and that derive from it. Recent studies have shown significant aspects of neuroblastoma heterogeneity that may affect the diagnostic-therapeutic strategy. Therefore, we developed a laboratory protocol, based on the combination of the advanced dielectrophoresis-based array technology and next-generation sequencing to identify and sort single cells individually and carry out their copy number variants analysis. The aim was to evaluate the cellular heterogeneity, avoiding overestimation or underestimation errors, due to a bulk analysis of the sample. We tested the above-mentioned protocol on two neuroblastoma cell lines, SK-N-BE(2)-C and IMR-32. The presence of several gain or loss chromosomal regions, in both cell lines, shows a high heterogeneity of the copy number variants status of the single tumor cells, even if they belong to an immortalized cell line. This finding confirms that each cell can potentially accumulate different alterations that can modulate its behavior. The laboratory protocol proposed herein provides a tool able to identify prevalent behaviors, and at the same time highlights the presence of particular clusters that deviate from them. Finally, it could be applicable to many other types of cancer.
Databáze: OpenAIRE
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