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Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80-540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.
Pubmed ID: 31304977 RIS Download
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Conversion software that both demultiplexes data and converts BCL files generated by Illumina sequencing systems to standard FASTQ file formats for downstream analysis.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsA software package for visualizing data and information. It visualizes data in a circular layout - this makes Circos ideal for exploring relationships between objects or positions.
View all literature mentionsCell line SK-N-FI is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line IMR-5/75 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BE(2)-C/ADR(5) is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line GI-ME-N is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SH-EP is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsA software package for visualizing data and information. It visualizes data in a circular layout - this makes Circos ideal for exploring relationships between objects or positions.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsConversion software that both demultiplexes data and converts BCL files generated by Illumina sequencing systems to standard FASTQ file formats for downstream analysis.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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