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; Koichi Matsuda

doi:10.1038/s41467-019-13286-z

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 OdaDaisuke Matsubara, Masashi Fujita, Tatsuhiro Shibata, Hidewaki Nakagawa, Robert Nakayama, Tadashi Kondo, Seiya Imoto, Satoru Miyano, Akira Kawai, Rui Yamaguchi, Hitoshi Ichikawa, Koichi Matsuda

Department of Basic Medicine

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35 Citations (Scopus)

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.

Original language	English
Article number	5683
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13286-z
Publication status	Published - Dec 1 2019

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-019-13286-z

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Hirata, M., Asano, N., Katayama, K., Yoshida, A., Tsuda, Y., Sekimizu, M., Mitani, S., Kobayashi, E., Komiyama, M., Fujimoto, H., Goto, T., Iwamoto, Y., Naka, N., Iwata, S., Nishida, Y., Hiruma, T., Hiraga, H., Kawano, H., Motoi, T., ... Matsuda, K. (2019). Integrated exome and RNA sequencing of dedifferentiated liposarcoma. Nature communications, 10(1), Article 5683. https://doi.org/10.1038/s41467-019-13286-z

Hirata, M, Asano, N, Katayama, K, Yoshida, A, Tsuda, Y, Sekimizu, M, Mitani, S, Kobayashi, E, Komiyama, M, Fujimoto, H, Goto, T, Iwamoto, Y, Naka, N, Iwata, S, Nishida, Y, Hiruma, T, Hiraga, H, Kawano, H, Motoi, T, Oda, Y, Matsubara, D, Fujita, M, Shibata, T, Nakagawa, H, Nakayama, R, Kondo, T, Imoto, S, Miyano, S, Kawai, A, Yamaguchi, R, Ichikawa, H & Matsuda, K 2019, 'Integrated exome and RNA sequencing of dedifferentiated liposarcoma', Nature communications, vol. 10, no. 1, 5683. https://doi.org/10.1038/s41467-019-13286-z

@article{00db0db25d09422bb8d73f4b317834fb,

title = "Integrated exome and RNA sequencing of dedifferentiated liposarcoma",

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.",

author = "Makoto Hirata and Naofumi Asano and Kotoe Katayama and Akihiko Yoshida and Yusuke Tsuda and Masaya Sekimizu and Sachiyo Mitani and Eisuke Kobayashi and Motokiyo Komiyama and Hiroyuki Fujimoto and Takahiro Goto and Yukihide Iwamoto and Norifumi Naka and Shintaro Iwata and Yoshihiro Nishida and Toru Hiruma and Hiroaki Hiraga and Hirotaka Kawano and Toru Motoi and Yoshinao Oda and Daisuke Matsubara and Masashi Fujita and Tatsuhiro Shibata and Hidewaki Nakagawa and Robert Nakayama and Tadashi Kondo and Seiya Imoto and Satoru Miyano and Akira Kawai and Rui Yamaguchi and Hitoshi Ichikawa and Koichi Matsuda",

note = "Funding Information: We express our gratitude to all the participants and collaborators in the Japan Sarcoma Genome Consortium. We thank Satoyo Oda and Akane Sei for their technical and administrative support. We also thank Dr. Nobuyuki Hashimoto and Dr. Nobuto Araki for supporting the sample collection in Osaka International Cancer Institute. This study was supported by KAKENHI (16H02676) of Japan Society of Promotion of Science; by the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) from Japan Agency for Medical Research and Development (AMED) (15cm0106141h0002 and 15cm0106142h0002); by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED (16cm0106520h0001 and 18cm0106535h0001); by Grants-in-Aid for Practical Research for Innovative Cancer Control from AMED (16ck0106089h003 and 18cm0106535h0001); by National Cancer Center Research and Development Funds (26-A-1 and 26-A-3), and by the Takeda Science Foundation. The super-computing resource was provided by Human Genome Center, the Institute of Medical Science, the University of Tokyo. Funding Information: Patients and tumor samples. We collected matched pairs of frozen normal and tumor samples from 65 patients (28 in JSGC-IMSUT and 37 in JSGC-NCC) with dedifferentiated liposarcoma (DDLPS). We also obtained WD components from 8 of the 65 DDLPS samples. We used blood, skin, or adipose tissue as the germline control samples. All of the samples collected from JSGC-IMSUT were transferred to a core analytic facility after anonymization at each hospital. Other samples that were collected from JSGC-NCC were prepared for next-generation sequencing at the National Cancer Center Research Institute. The frozen tumor samples from JSGC-IMSUT were sectioned for histological evaluation (Supplementary Fig. 13) and extraction of DNA and RNA. Histological data from the frozen and formalin-fixed paraffin-embedded tumor samples, which had been prepared for clinical diagnosis, were evaluated by musculoskeletal pathologists to confirm the diagnosis and validity of the tumors and also to examine the content of the tumor cells. The present protocols were reviewed and approved by the Ethics Committees of all participating institutions, including the Institute of Medical Science, the University of Tokyo, the National Cancer Center, Japan, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Kyushu University, Osaka International Cancer Institute, Chiba Cancer Center, Nagoya University Graduate School of Medicine, Kanagawa Cancer Center, National Hospital Organization Hokkaido Cancer Center, and RIKEN Center for Integrative Medical Sciences. All of the participants were enrolled and anonymised after approval by the institutional review board. We obtained written informed consent from all participants, except for those we could not contact due to loss of follow-up or death at registration. In these cases, the Institutional Review Boards at each participating institution granted permission for existing tissue samples to be used for research purposes. In addition, the Institutional Review Board of the Institute of Medical Science, University of Tokyo provided permission for the fully anonymised genetic data to be shared (protocol numbers 26-22-0630 and 30-78-B0305). None of the samples used in this study came from patients who had opted out of participation. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13286-z",

language = "English",

volume = "10",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Integrated exome and RNA sequencing of dedifferentiated liposarcoma

AU - Hirata, Makoto

AU - Asano, Naofumi

AU - Katayama, Kotoe

AU - Yoshida, Akihiko

AU - Tsuda, Yusuke

AU - Sekimizu, Masaya

AU - Mitani, Sachiyo

AU - Kobayashi, Eisuke

AU - Komiyama, Motokiyo

AU - Fujimoto, Hiroyuki

AU - Goto, Takahiro

AU - Iwamoto, Yukihide

AU - Naka, Norifumi

AU - Iwata, Shintaro

AU - Nishida, Yoshihiro

AU - Hiruma, Toru

AU - Hiraga, Hiroaki

AU - Kawano, Hirotaka

AU - Motoi, Toru

AU - Oda, Yoshinao

AU - Matsubara, Daisuke

AU - Fujita, Masashi

AU - Shibata, Tatsuhiro

AU - Nakagawa, Hidewaki

AU - Nakayama, Robert

AU - Kondo, Tadashi

AU - Imoto, Seiya

AU - Miyano, Satoru

AU - Kawai, Akira

AU - Yamaguchi, Rui

AU - Ichikawa, Hitoshi

AU - Matsuda, Koichi

N1 - Funding Information: We express our gratitude to all the participants and collaborators in the Japan Sarcoma Genome Consortium. We thank Satoyo Oda and Akane Sei for their technical and administrative support. We also thank Dr. Nobuyuki Hashimoto and Dr. Nobuto Araki for supporting the sample collection in Osaka International Cancer Institute. This study was supported by KAKENHI (16H02676) of Japan Society of Promotion of Science; by the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) from Japan Agency for Medical Research and Development (AMED) (15cm0106141h0002 and 15cm0106142h0002); by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED (16cm0106520h0001 and 18cm0106535h0001); by Grants-in-Aid for Practical Research for Innovative Cancer Control from AMED (16ck0106089h003 and 18cm0106535h0001); by National Cancer Center Research and Development Funds (26-A-1 and 26-A-3), and by the Takeda Science Foundation. The super-computing resource was provided by Human Genome Center, the Institute of Medical Science, the University of Tokyo. Funding Information: Patients and tumor samples. We collected matched pairs of frozen normal and tumor samples from 65 patients (28 in JSGC-IMSUT and 37 in JSGC-NCC) with dedifferentiated liposarcoma (DDLPS). We also obtained WD components from 8 of the 65 DDLPS samples. We used blood, skin, or adipose tissue as the germline control samples. All of the samples collected from JSGC-IMSUT were transferred to a core analytic facility after anonymization at each hospital. Other samples that were collected from JSGC-NCC were prepared for next-generation sequencing at the National Cancer Center Research Institute. The frozen tumor samples from JSGC-IMSUT were sectioned for histological evaluation (Supplementary Fig. 13) and extraction of DNA and RNA. Histological data from the frozen and formalin-fixed paraffin-embedded tumor samples, which had been prepared for clinical diagnosis, were evaluated by musculoskeletal pathologists to confirm the diagnosis and validity of the tumors and also to examine the content of the tumor cells. The present protocols were reviewed and approved by the Ethics Committees of all participating institutions, including the Institute of Medical Science, the University of Tokyo, the National Cancer Center, Japan, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Kyushu University, Osaka International Cancer Institute, Chiba Cancer Center, Nagoya University Graduate School of Medicine, Kanagawa Cancer Center, National Hospital Organization Hokkaido Cancer Center, and RIKEN Center for Integrative Medical Sciences. All of the participants were enrolled and anonymised after approval by the institutional review board. We obtained written informed consent from all participants, except for those we could not contact due to loss of follow-up or death at registration. In these cases, the Institutional Review Boards at each participating institution granted permission for existing tissue samples to be used for research purposes. In addition, the Institutional Review Board of the Institute of Medical Science, University of Tokyo provided permission for the fully anonymised genetic data to be shared (protocol numbers 26-22-0630 and 30-78-B0305). None of the samples used in this study came from patients who had opted out of participation. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-019-13286-z

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VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

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ER -

Integrated exome and RNA sequencing of dedifferentiated liposarcoma

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