Pathological and genomic analyses of uterine sarcoma by next generation sequencing

• Project/Area Number: 19K07433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kanazawa University (2021); Osaka University (2019-2020)
• Principal Investigator: Daichi Maeda 金沢大学, 医学系, 教授 (30585500)
• Co-Investigator(Kenkyū-buntansha): 後藤 明輝 秋田大学, 医学系研究科, 教授 (90317090)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 子宮肉腫 / 子宮間葉系腫瘍

Outline of Research at the Start

子宮肉腫の遺伝子変異、融合遺伝子を検出するにあたって、次世代シーケンサー(NGS)を活用する。まず、独自の技術を用いて既知の子宮肉腫関連の遺伝子異常を網羅する遺伝子パネルを構築し、約80例の子宮肉腫ホルマリン固定検体を対象にターゲットシーケンスを行う。並行して凍結検体を用いた全ゲノム解析を施行し、新規遺伝子異常の同定を目指す。これらを統合して子宮肉腫のgenomic landscapeを描く。

Outline of Final Research Achievements

Genetic background of the uterine sarcomas remain largely unknown. Furthermore, there has been confusion regarding histological classification of there rare tumors. In this study, we utilized next generation sequencing to reveal mutations and fusion genes involved in the tumorigenesis of uterine sarcoma. We developed a gene panel that covers a large number of genes that are known to be altered in uterine sarcomas and applied it to actual cases. As a result, we identified uterine low-grade endometrial stromal sarcoma harboring JAZF1 fusion gene, and also a sarcoma that harbors GREB1 fusion. These findings would lead to elucidation of the genetic landscape of uterine sarcomas.

Academic Significance and Societal Importance of the Research Achievements

子宮肉腫の成り立ちを背景遺伝子異常の観点から整理し、より正確な病理診断を可能とすることで、適切な治療への誘導が可能になると考えられる。子宮肉腫に関しては様々な融合遺伝子の存在が知られるようになってきている。我々が開発した遺伝子パネルはその多くをカバーするもので、それを用いて今後、多数例の検討を行うことで、日本人の子宮肉腫の全貌を明らかにしていくことが可能だと考えいてる。

Research Products

• [Journal Article] Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications (2022)
  • Author(s): Akiyama Yoshiyuki、Miyakawa Jimpei、O’Donnell Michael A.、Kreder Karl J.、Luo Yi、Maeda Daichi、Ushiku Tetsuo、Kume Haruki、Homma Yukio
  • Journal Title: Journal of Urology Volume: 207 Issue: 3 Pages: 635-646
  • DOI: 10.1097/ju.0000000000002278
• [Journal Article] Disorganization of intercalated discs in dilated cardiomyopathy (2021)
  • Author(s): Ito Yukinobu、Yoshida Makoto、Masuda Hirotake、Maeda Daichi、Kudo-Asabe Yukitsugu、Umakoshi Michinobu、Nanjo Hiroshi、Goto Akiteru
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 11852-11852
  • DOI: 10.1038/s41598-021-90502-1
  • Peer Reviewed / Open Access
• [Journal Article] Detection of MED12 mutations in mesenchymal components of uterine adenomyomas (2021)
  • Author(s): Kito Masahiko、Maeda Daichi、Kudo-Asabe Yukitsugu、Tamura Daisuke、Makino Kenichi、Sageshima Masato、Nanjo Hiroshi、Terada Yukihiro、Goto Akiteru
  • Journal Title: Human Pathology Volume: 109 Pages: 31-36
  • DOI: 10.1016/j.humpath.2020.11.013
  • Peer Reviewed
• [Journal Article] Severe Abdominal Recurrence of Low-grade Endometrial Stromal Sarcoma After Hysteroscopic Surgery (2021)
  • Author(s): TAMURA DAISUKE、MAEDA DAICHI、ENOMOTO KATSUHIKO、SATO HIROKAZU
  • Journal Title: Anticancer Research Volume: 41 Issue: 8 Pages: 4013-4016
  • DOI: 10.21873/anticanres.15199
  • Peer Reviewed
• [Journal Article] Comprehensive immunohistochemical analysis of the gastrointestinal and M?llerian phenotypes of 139 ovarian mucinous cystadenomas (2021)
  • Author(s): Halimi Sultan Ahmad、Maeda Daichi、Ushiku-Shinozaki Aya、Goto Akiteru、Oda Katsutoshi、Osuga Yutaka、Fujii Tomoyuki、Ushiku Tetsuo、Fukayama Masashi
  • Journal Title: Human Pathology Volume: 109 Pages: 21-30
  • DOI: 10.1016/j.humpath.2020.11.011
  • Peer Reviewed
• [Journal Article] E74-Like Factor 3 Is a Key Regulator of Epithelial Integrity and Immune Response Genes in Biliary Tract Cancer (2020)
  • Author(s): Suzuki Masami、Saito-Adachi Mihoko、Arai Yasuhito、Fujiwara Yuko、Takai Erina、Shibata Shinsuke、Seki Masahide、Rokutan Hirofumi、Maeda Daichi、Horie Masafumi、Suzuki Yutaka、Shibata Tatsuhiro、Kiyono Tohru、Yachida Shinichi
  • Journal Title: Cancer Research Volume: 81 Issue: 2 Pages: 489-500
  • DOI: 10.1158/0008-5472.can-19-2988
  • Peer Reviewed / Open Access
• [Journal Article] Myoepithelioma-like Hyalinizing Epithelioid Tumor of the Foot Harboring an OGT-FOXO1 Fusion (2020)
  • Author(s): Yorozu Takashi、Nagahama Kiyotaka、Morii Takeshi、Maeda Daichi、Yoshida Akihiko、Mori Taisuke、Hayashi Akimasa、Shibahara Junji
  • Journal Title: American Journal of Surgical Pathology Volume: 45 Issue: 2 Pages: 287-290
  • DOI: 10.1097/pas.0000000000001539
  • Open Access
• [Journal Article] Detection of MEAF6‐PHF1 translocation in an endometrial stromal nodule (2020)
  • Author(s): Nomura Yusuke、Tamura Daisuke、Horie Masafumi、Sato Masakazu、Sasaki Shinya、Yamamoto Yohei、Kudo‐Asabe Yukitsugu、Umakoshi Michinobu、Koyama Kei、Makino Kenichi、Takashima Shinogu、Imai Kazuhiro、Minamiya Yoshihiro、Munakata Satoru、Yachida Shinichi、Terada Yukihiro、Goto Akiteru、Maeda Daichi
  • Journal Title: Genes, Chromosomes and Cancer Volume: 59 Issue: 12 Pages: 702-708
  • DOI: 10.1002/gcc.22892
  • NAID: 120007089057
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological and molecular analyses of linearly expanded epithelial cells with β‐catenin alterations, “β‐catenin signature”, in the normal fallopian tube (2020)
  • Author(s): Koyama Kei、Maeda Daichi、Kito Masahiko、Tamura Daisuke、Kudo‐Asabe Yukitsugu、Katoh Hiroto、Ishikawa Shumpei、Nanjo Hiroshi、Terada Yukihiro、Goto Akiteru
  • Journal Title: Histopathology Volume: 77 Issue: 6 Pages: 880-889
  • DOI: 10.1111/his.14227
  • Peer Reviewed / Open Access
• [Journal Article] Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia (2020)
  • Author(s): Baba S, Taguchi A, Kawata A, Hara K, Eguchi S, Mori M, Adachi K, Mori S, Iwata T, Mitsuhashi A, Maeda D, Komatsu A, Nagamatsu T, Oda K, Kukimoto I, Osuga Y, Fujii T, Kawana K.
  • Journal Title: Virol J Volume: 17 Issue: 1 Pages: 32-32
  • DOI: 10.1186/s12985-020-01306-0
  • NAID: 120007089054
  • Peer Reviewed / Open Access
• [Journal Article] Post-mortem Plasma Cell-Free DNA Sequencing: Proof-of-Concept Study for the "Liquid Autopsy". (2020)
  • Author(s): Ito Y, Yoshida M, Inoue T, Habuchi T, Ikoma S, Katoh H, Kato M, Shibata T, Ishikawa S, Yachida S, Goto A.
  • Journal Title: Sci Rep Volume: 10(1) Issue: 1 Pages: 2120-2120
  • DOI: 10.1038/s41598-020-59193-y
  • NAID: 120007089050
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An extragonadal yolk sac tumor presumed to be of postmeiotic germ cell origin by genetic zygosity analysis via single nucleotide polymorphism array (2019)
  • Author(s): Tamura Daisuke、Maeda Daichi、Sato Toshiharu、Sugawara Tae、Shirasawa Hiromitsu、Shimizu Dai、Sato Naoki、Goto Akiteru、Terada Yukihiro
  • Journal Title: Genes, Chromosomes and Cancer Volume: 59 Issue: 3 Pages: 209-213
  • DOI: 10.1002/gcc.22817
  • NAID: 120007089058
  • Peer Reviewed / Open Access
• [Journal Article] Safety and efficacy of mucosal immunotherapy using human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): the study protocol of a randomized placebo-controlled clinical trial (MILACLE study), (2019)
  • Author(s): Ikeda Y, Uemura Y, Asai-Sato M, Nakao T, Nakajima T, Iwata T, Akiyama A, Satoh T, Yahata H, Kato K, Maeda D, Aoki D, Kawana K
  • Journal Title: Jap J Clin Oncol, Volume: 49(9) Issue: 9 Pages: 877-880
  • DOI: 10.1093/jjco/hyz095
  • Peer Reviewed / Open Access
• [Journal Article] Gallbladder cancer harboring ERBB2 mutation on the primary and metastatic site: A case report (2019)
  • Author(s): Inagaki Chiaki、Maeda Daichi、Kimura Akie、Otsuru Toru、Iwagami Yoshifumi、Nishida Naohiro、Sakai Daisuke、Shitotsuki Ryo、Yachida Shinichi、Doki Yuichiro、Satoh Taroh
  • Journal Title: World Journal of Gastrointestinal Oncology Volume: 11 Issue: 9 Pages: 761-767
  • DOI: 10.4251/wjgo.v11.i9.761
  • NAID: 120007089055
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of Tattoo Pigment in Lymph Nodes Dissected for Gynecological Malignancy (2019)
  • Author(s): Tamura Daisuke、Maeda Daichi、Terada Yukihiro、Goto Akiteru
  • Journal Title: International Journal of Surgical Pathology Volume: 27 Issue: 7 Pages: 773-777
  • DOI: 10.1177/1066896919846395
  • Peer Reviewed
• [Journal Article] Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies (2019)
  • Author(s): Akiyama Yoshiyuki、Maeda Daichi、Katoh Hiroto、Morikawa Teppei、Niimi Aya、Nomiya Akira、Sato Yusuke、Kawai Taketo、Goto Akiteru、Fujimura Tetsuya、Fukuhara Hiroshi、Nakagawa Tohru、Igawa Yasuhiko、Ishikawa Shumpei、Fukayama Masashi、Kume Haruki、Homma Yukio
  • Journal Title: Journal of Urology Volume: 印刷中 Issue: 2 Pages: 290-300
  • DOI: 10.1097/ju.0000000000000234
  • Peer Reviewed / Int'l Joint Research