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Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma

Author

Listed:
  • Osamu Gotoh

    (Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research)

  • Yuko Sugiyama

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Yutaka Takazawa

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Kazuyoshi Kato

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Norio Tanaka

    (Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research)

  • Kohei Omatsu

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Nobuhiro Takeshima

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Hidetaka Nomura

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Kosei Hasegawa

    (Saitama Medical University International Medical Center)

  • Keiichi Fujiwara

    (Saitama Medical University International Medical Center)

  • Mana Taki

    (Kyoto University Hospital)

  • Noriomi Matsumura

    (Kyoto University Hospital)

  • Tetsuo Noda

    (Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research)

  • Seiichi Mori

    (Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research)

Abstract

Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.

Suggested Citation

  • Osamu Gotoh & Yuko Sugiyama & Yutaka Takazawa & Kazuyoshi Kato & Norio Tanaka & Kohei Omatsu & Nobuhiro Takeshima & Hidetaka Nomura & Kosei Hasegawa & Keiichi Fujiwara & Mana Taki & Noriomi Matsumura , 2019. "Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12985-x
    DOI: 10.1038/s41467-019-12985-x
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    Cited by:

    1. Kosuke Tomimatsu & Takeru Fujii & Ryoma Bise & Kazufumi Hosoda & Yosuke Taniguchi & Hiroshi Ochiai & Hiroaki Ohishi & Kanta Ando & Ryoma Minami & Kaori Tanaka & Taro Tachibana & Seiichi Mori & Akihito, 2024. "Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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