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

International Journal of Molecular Sciences
Federica CariatiRossella Tomaiuolo

Abstract

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 part...Continue Reading

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Citations

Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Amparo López-CarrascoRosa Noguera

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Methods Mentioned

BETA
Assay
biopsy

Software Mentioned

CellBrowser
VeriSeq
BlueFuse Multi Software

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