The DOI matches its Crossref record; 70 of the 71 references it cites were found in a registry or an index.
An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping
Open accessAbstract
Gastroenteropancreatic (GEP) neuroendocrine neoplasm (NEN) that consists of neuroendocrine tumor and neuroendocrine carcinoma (NEC) is a lethal but under-investigated disease owing to its rarity. To fill the scarcity of clinically relevant models of GEP-NEN, we here established 25 lines of NEN organoids and performed their comprehensive molecular characterization. GEP-NEN organoids recapitulated pathohistological and functional phenotypes of the original tumors. Whole-genome sequencing revealed frequent genetic alterations in TP53 and RB1 in GEP-NECs, and characteristic chromosome-wide loss of heterozygosity in GEP-NENs. Transcriptome analysis identified molecular subtypes that are distinguished by the expression of distinct transcription factors. GEP-NEN organoids gained independence from the stem cell niche irrespective of genetic mutations. Compound knockout of TP53 and RB1, together with overexpression of key transcription factors, conferred on the normal colonic epithelium phenotypes that are compatible with GEP-NEN biology. Altogether, our study not only provides genetic understanding of GEP-NEN, but also connects its genetics and biological phenotypes.
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“They showed that while cells from tumorspheres displayed a solid growth pattern, organoids were more diffusive, similar to the tumor of origin172.”
From Organoids (2022) · cites this paper as [172]
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“These tumoroid biobanks can then be used as in vitro models of tumorigenesis and offer a significant advantage over conventional 2D cell culture technology5,6.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [5]
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Metadata
- Authors
- Kawasaki, K., Toshimitsu, K., Matano, M., Fujita, M., Fujii, M., Togasaki, K., Ebisudani, T., Shimokawa, M., Takano, A., Takahashi, S., Ohta, Y., Nanki, K., Igarashi, R., Ishimaru, K., Ishida, H., Sukawa, Y., Sugimoto, S., Saito, Y., Maejima, K., Sasagawa, S., Lee, H., Kim, H.-G., Ha, K., Hamamoto, J., Fukunaga, K., Maekawa, A., Tanabe, M., Ishihara, S., Hamamoto, Y., Yasuda, H., Sekine, S., Kudo, A., Kitagawa, Y., Kanai, T., Nakagawa, H., & Sato, T.
- Affiliations
- Keio University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Seoul National University (KR)
- Tokyo Medical and Dental University (JP)
- The University of Tokyo (JP)
- National Cancer Center Hospital (JP)
- Corresponding author
- Sato, Toshiro
- ORCID
- Kawasaki, Kenta
- Matano, Mami
- Fujita, Masashi
- Fujii, Masayuki
- Togasaki, Kazuhiro
- Ebisudani, Toshiki
- Takano, Ai
- Takahashi, Sirirat
- Ohta, Yuki
- Nanki, Kosaku
- Ishimaru, Kazuhiro
- Sukawa, Yasutaka
- Sugimoto, Shinya
- Saito, Yoshimasa
- Kim, Hong-Gee
- Ha, Kyungsik
- Hamamoto, Junko
- Fukunaga, Koichi
- Maekawa, Aya
- Tanabe, Minoru
- Ishihara, Soichiro
- Hamamoto, Yasuo
- Yasuda, Hiroyuki
- Sekine, Shigeki
- Kudo, Atsushi
- Kitagawa, Yuko
- Nakagawa, Hidewaki
- Sato, Toshiro
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 183
- Issue
- 5
- Pages
- 1420-1435.e21
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W3097717913
- Cited by
- 238
- References
- 71
- Citations by year
- 2026: 35 · 2025: 48 · 2024: 40 · 2023: 39 · 2022: 38 · 2021: 28 · 2020: 1
- FWCI
- 19.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Japan Agency for Medical Research and Development (19cm010654, 20cm0106576, 20ck0106471, JP20cm0106206)
- Japan Society for the Promotion of Science (JP17H06176)
- Topics
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
- Keywords
- gastroenteropancreatic neuroendocrine tumors, neuroendocrine carcinoma, organoids, biobanks, genotype-phenotype mapping, TP53, RB1, loss of heterozygosity, transcription factors, molecular subtypes, colonic epithelium
- MeSH terms
- Whole Genome Sequencing, Animals, Chromosomes, Human, Genotype, Humans, Intestinal Neoplasms, Male, Models, Genetic, Mutation, Organoids, Pancreatic Neoplasms, Phenotype, Stomach Neoplasms, Biological Specimen Banks, Neuroendocrine Tumors, Intercellular Signaling Peptides and Proteins, Mice, Transcriptome
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