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Patient derived organoids to model rare prostate cancer phenotypes.

Loredana Puca | Rohan Bareja | Davide Prandi | Reid Shaw | Matteo Benelli | Wouter R Karthaus | Judy Hess | Michael Sigouros | Adam Donoghue | Myriam Kossai | Dong Gao | Joanna Cyrta | Verena Sailer | Aram Vosoughi | Chantal Pauli | Yelena Churakova | Cynthia Cheung | Lesa Dayal Deonarine | Terra J McNary | Rachele Rosati | Scott T Tagawa | David M Nanus | Juan Miguel Mosquera | Charles L Sawyers | Yu Chen | Giorgio Inghirami | Rema A Rao | Carla Grandori | Olivier Elemento | Andrea Sboner | Francesca Demichelis | Mark A Rubin | Himisha Beltran
Nature communications | 2018

A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.

Pubmed ID: 29921838

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA193837
  • Agency: NCI NIH HHS, United States
    Id: P50 CA092629
  • Agency: NCI NIH HHS, United States
    Id: U54 CA210184
  • Agency: NCI NIH HHS, United States
    Id: R01 CA155169
  • Agency: NCI NIH HHS, United States
    Id: R01 CA208100
  • Agency: NCI NIH HHS, United States
    Id: P50 CA211024
  • Agency: NCI NIH HHS, United States
    Id: U54 CA224079
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NCI NIH HHS, United States
    Id: K08 CA140946

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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Imaris (tool)

RRID:SCR_007370

Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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GENCODE (tool)

RRID:SCR_014966

Human and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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InvivoGen (tool)

RRID:SCR_026997

Biotechnology company in San Diego, California. Provides life scientists with innovative research reagents including immunity and cell culture products.

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