Integrated exome and RNA sequencing of dedifferentiated liposarcoma

Makoto Hirata, Naofumi Asano, Kotoe Katayama, Akihiko Yoshida, Yusuke Tsuda, Masaya Sekimizu, Sachiyo Mitani, Eisuke Kobayashi, Motokiyo Komiyama, Hiroyuki Fujimoto, Takahiro Goto, Yukihide Iwamoto, Norifumi Naka, Shintaro Iwata, Yoshihiro Nishida, Toru Hiruma, Hiroaki Hiraga, Hirotaka Kawano, Toru Motoi, Yoshinao Oda, Daisuke Matsubara, Masashi Fujita, Tatsuhiro Shibata, Hidewaki Nakagawa, Robert Nakayama, Tadashi Kondo, Seiya Imoto, Satoru Miyano, Akira Kawai, Rui Yamaguchi (), Hitoshi Ichikawa () and Koichi Matsuda ()
Additional contact information
Makoto Hirata: University of Tokyo
Naofumi Asano: National Cancer Center Research Institute
Kotoe Katayama: University of Tokyo
Akihiko Yoshida: National Cancer Center Hospital
Yusuke Tsuda: University of Tokyo
Masaya Sekimizu: National Cancer Center Research Institute
Sachiyo Mitani: National Cancer Center Research Institute
Eisuke Kobayashi: National Cancer Center Hospital
Motokiyo Komiyama: National Cancer Center Hospital
Hiroyuki Fujimoto: National Cancer Center Hospital
Takahiro Goto: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Yukihide Iwamoto: Kyushu University
Norifumi Naka: Osaka International Cancer Institute
Shintaro Iwata: National Cancer Center Hospital
Yoshihiro Nishida: Nagoya University Graduate School of Medicine
Toru Hiruma: Kanagawa Cancer Center
Hiroaki Hiraga: National Hospital Organization Hokkaido Cancer Center
Hirotaka Kawano: University of Tokyo
Toru Motoi: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Yoshinao Oda: Kyushu University
Daisuke Matsubara: Jichi Medical University
Masashi Fujita: RIKEN Center for Integrative Medical Sciences
Tatsuhiro Shibata: University of Tokyo
Hidewaki Nakagawa: RIKEN Center for Integrative Medical Sciences
Robert Nakayama: Keio University School of Medicine
Tadashi Kondo: National Cancer Center Research Institute
Seiya Imoto: University of Tokyo
Satoru Miyano: University of Tokyo
Akira Kawai: National Cancer Center Hospital
Rui Yamaguchi: University of Tokyo
Hitoshi Ichikawa: National Cancer Center Research Institute
Koichi Matsuda: University of Tokyo

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13286-z

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