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ヒグチ リヨウタ
Higuchi Riyouta
樋口 亮太 所属 医学部 医学科（附属八千代医療センター） 職種 講師 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読なし |
| 表題 | Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System. |
| 掲載誌名 | 正式名：Cancer discovery 略 称：Cancer Discov ISSNコード：21598290/21598274 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 12(3),pp.692-711 |
| 著者・共著者 | Yachida Shinichi, Totoki Yasushi, Noë Michaël, Nakatani Yoichiro, Horie Masafumi, Kawasaki Kenta, Nakamura Hiromi, Saito-Adachi Mihoko, Suzuki Masami, Takai Erina, Hama Natsuko, Higuchi Ryota, Hirono Seiko, Shiba Satoshi, Kato Mamoru, Furukawa Eisaku, Arai Yasuhito, Rokutan Hirofumi, Hashimoto Taiki, Mitsunaga Shuichi, Kanda Mitsuro, Tanaka Hidenori, Takata So, Shimomura Ayaka, Oshima Minoru, Hackeng Wenzel M, Okumura Tomoyuki, Okano Keiichi, Yamamoto Masakazu, Yamaue Hiroki, Morizane Chigusa, Arihiro Koji, Furukawa Toru, Sato Toshiro, Kiyono Tohru, Brosens Lodewijk A A, Wood Laura D, Hruban Ralph H, Shibata Tatsuhiro |
| 発行年月 | 2022/03 |
| 概要 | The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer.SIGNIFICANCE:GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587. |
| DOI | 10.1158/2159-8290.CD-21-0669 |
| PMID | 34880079 |