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Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System.
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.
Afiliação
  • Yachida S; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Totoki Y; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
  • Noë M; Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan.
  • Nakatani Y; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Horie M; Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
  • Kawasaki K; Sol Goldman Pancreatic Cancer Research Center, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
  • Nakamura H; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Saito-Adachi M; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Suzuki M; Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Takai E; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Hama N; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Higuchi R; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Hirono S; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Shiba S; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Kato M; Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
  • Furukawa E; Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
  • Arai Y; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Rokutan H; Department of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan.
  • Hashimoto T; Department of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan.
  • Mitsunaga S; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Kanda M; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Tanaka H; Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
  • Takata S; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan.
  • Shimomura A; Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Aichi, Japan.
  • Oshima M; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Hackeng WM; Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Okumura T; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Okano K; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Yamamoto M; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Yamaue H; Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
  • Morizane C; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Arihiro K; Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
  • Furukawa T; Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
  • Sato T; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
  • Kiyono T; Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
  • Brosens LAA; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
  • Wood LD; Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Hruban RH; Project for Prevention of HPV-Related Cancer, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
  • Shibata T; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Cancer Discov ; 12(3): 692-711, 2022 03 01.
Article em En | MEDLINE | ID: mdl-34880079
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tumores Neuroendócrinos / Carcinoma Neuroendócrino Limite: Humans / Newborn Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tumores Neuroendócrinos / Carcinoma Neuroendócrino Limite: Humans / Newborn Idioma: En Ano de publicação: 2022 Tipo de documento: Article