日庆应义塾大学Toshiro Sato小组构建了神经内分泌肿瘤的类器官生物库。2020年11月6日，国际知名学术期刊《细胞》在线发表了这一成果。

Title: An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping

Author: Kenta Kawasaki, Kohta Toshimitsu, Mami Matano, Masashi Fujita, Masayuki Fujii, Kazuhiro Togasaki, Toshiki Ebisudani, Mariko Shimokawa, Ai Takano, Sirirat Takahashi, Yuki Ohta, Kosaku Nanki, Ryo Igarashi, Kazuhiro Ishimaru, Hiroki Ishida, Yasutaka Sukawa, Shinya Sugimoto, Yoshimasa Saito, Kazuhiro Maejima, Shota Sasagawa, Hwajin Lee, Hong-Gee Kim, Kyungsik Ha, Junko Hamamoto, Koichi Fukunaga, Aya Maekawa, Minoru Tanabe, Soichiro Ishihara, Yasuo Hamamoto, Hiroyuki Yasuda, Shigeki Sekine, Atsushi Kudo, Yuko Kitagawa, Takanori Kanai, Hidewaki Nakagawa, Toshiro Sato

Issue&Volume: 2020-11-06

Abstract: Gastroenteropancreatic (GEP) neuroendocrine neoplasm (NEN) that consists of neuroendocrinetumor 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 molecularcharacterization. GEP-NEN organoids recapitulated pathohistological and functionalphenotypes of the original tumors. Whole-genome sequencing revealed frequent geneticalterations 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 theexpression of distinct transcription factors. GEP-NEN organoids gained independencefrom the stem cell niche irrespective of genetic mutations. Compound knockout of TP53and RB1, together with overexpression of key transcription factors, conferred on thenormal colonic epithelium phenotypes that are compatible with GEP-NEN biology. Altogether,our study not only provides genetic understanding of GEP-NEN, but also connects itsgenetics and biological phenotypes.

DOI: 10.1016/j.cell.2020.10.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31387-8