Abstract

The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.

Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

Details

Title
Integrated exome and RNA sequencing of dedifferentiated liposarcoma
Author
Hirata Makoto 1   VIAFID ORCID Logo  ; Asano Naofumi 2 ; Katayama Kotoe 3 ; Yoshida Akihiko 4   VIAFID ORCID Logo  ; Tsuda Yusuke 5 ; Sekimizu Masaya 6 ; Mitani Sachiyo 6 ; Kobayashi Eisuke 7 ; Komiyama Motokiyo 8 ; Fujimoto Hiroyuki 8 ; Goto Takahiro 9 ; Iwamoto Yukihide 10 ; Naka Norifumi 11 ; Iwata Shintaro 12 ; Nishida Yoshihiro 13 ; Hiruma Toru 14 ; Hiraga Hiroaki 15 ; Kawano Hirotaka 16 ; Motoi Toru 17 ; Oda Yoshinao 18 ; Matsubara Daisuke 19 ; Fujita Masashi 20   VIAFID ORCID Logo  ; Shibata Tatsuhiro 21 ; Nakagawa Hidewaki 22 ; Nakayama, Robert 23 ; Kondo Tadashi 24 ; Imoto Seiya 25   VIAFID ORCID Logo  ; Miyano Satoru 26 ; Kawai Akira 7 ; Yamaguchi, Rui 26 ; Ichikawa Hitoshi 27   VIAFID ORCID Logo  ; Matsuda Koichi 28   VIAFID ORCID Logo 

1  University of Tokyo, Laboratory of Genome Technology, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
2  National Cancer Center Research Institute, Division of Rare Cancer Research, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385); Keio University School of Medicine, Department of Orthopaedic Surgery, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959) 
3  University of Tokyo, Laboratory of Sequence Analysis, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
4  National Cancer Center Hospital, Department of Pathology and Clinical Laboratory, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
5  University of Tokyo, Laboratory of Genome Technology, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); University of Tokyo, Department of Orthopaedic Surgery, Faculty of Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
6  National Cancer Center Research Institute, Department of Clinical Genomics, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
7  National Cancer Center Hospital, Department of Musculoskeletal Oncology, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
8  National Cancer Center Hospital, Department of Urology, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
9  Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Department of Orthopaedic Surgery and Musculoskeletal Oncology, Tokyo, Japan (GRID:grid.415479.a) 
10  Kyushu University, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849); Kyushu Rosai Hospital, Kitakyushu, Japan (GRID:grid.415645.7) (ISNI:0000 0004 0378 8112) 
11  Osaka International Cancer Institute, Musculoskeletal Oncology Service, Osaka, Japan (GRID:grid.489169.b) 
12  National Cancer Center Hospital, Department of Musculoskeletal Oncology, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385); Chiba Cancer Center, Division of Orthopaedic Surgery, Chiba, Japan (GRID:grid.418490.0) (ISNI:0000 0004 1764 921X) 
13  Nagoya University Graduate School of Medicine, Department of Rehabilitation Medicine, Nagoya, Japan (GRID:grid.27476.30) (ISNI:0000 0001 0943 978X) 
14  Kanagawa Cancer Center, Department of Orthopaedic Surgery, Yokohama, Japan (GRID:grid.414944.8) (ISNI:0000 0004 0629 2905) 
15  National Hospital Organization Hokkaido Cancer Center, Department of Musculoskeletal Oncology, Sapporo, Japan (GRID:grid.415270.5) 
16  University of Tokyo, Department of Orthopaedic Surgery, Faculty of Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Teikyo University School of Medicine, Department of Orthopaedic Surgery, Tokyo, Japan (GRID:grid.264706.1) (ISNI:0000 0000 9239 9995) 
17  Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Department of Pathology, Tokyo, Japan (GRID:grid.415479.a) 
18  Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
19  Jichi Medical University, Division of Integrative Pathology, Shimotsuke, Japan (GRID:grid.410804.9) (ISNI:0000000123090000) 
20  RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics, Yokohama, Japan (GRID:grid.410804.9) 
21  University of Tokyo, Laboratory of Molecular Medicine, Institiute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
22  RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics, Yokohama, Japan (GRID:grid.26999.3d) 
23  Keio University School of Medicine, Department of Orthopaedic Surgery, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959) 
24  National Cancer Center Research Institute, Division of Rare Cancer Research, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
25  University of Tokyo, Division of Health Medical Data Science, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
26  University of Tokyo, Laboratory of DNA Information Analysis, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
27  National Cancer Center Research Institute, Department of Clinical Genomics, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385); National Cancer Center-Exploratory Oncology Research & Clinical Trial Center, Division of Translational Genomics, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
28  University of Tokyo, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13286-z
ProQuest document ID
2325293264
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.