Asano, Naofumi

写真a

Affiliation

School of Medicine, Department of Orthopaedic Surgery （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework, 2017.03

    Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma

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Licenses and Qualifications 【 Display / hide 】

  • Orthopedic specialist, 2011.03

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Research Areas 【 Display / hide 】

  • Life Science / Orthopedics

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Research Keywords 【 Display / hide 】

  • bone and soft tissue tumor, sarcoma

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Papers 【 Display / hide 】

  • A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes

    Asano N., Matsuzaki J., Ichikawa M., Kawauchi J., Takizawa S., Aoki Y., Sakamoto H., Yoshida A., Kobayashi E., Tanzawa Y., Nakayama R., Morioka H., Matsumoto M., Nakamura M., Kondo T., Kato K., Tsuchiya N., Kawai A., Ochiya T.

    Nature Communications （Nature Communications)  10 （ 1 ）  2019.12

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    © 2019, The Author(s). Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival.

  • Pseudomyogenic hemangioendothelioma of bone treated with denosumab: A case report

    Otani S., Nakayama R., Sekita T., Hirozane T., Asano N., Nishimoto K., Sasaki A., Okita H., Morioka H., Nakamura M., Matsumoto M.

    BMC Cancer （BMC Cancer)  19 （ 1 ）  2019.09

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    © 2019 The Author(s). Background: Pseudomyogenic hemangioendothelioma (PMHE) is a rare endothelial neoplasm that involves the bones in only 14% of all cases. The optimal treatment strategy has not been established. We herein report a case of primary PMHE in which denosumab treatment showed activity in both imaging studies and the clinical outcome. Case presentation: A 20-year-old woman presented with worsening pain in her left ankle. Imaging studies showed multifocal fluorodeoxyglucose (FDG)-avid [maximum standardized uptake value (SUVmax), 15.95] osteolytic lesions in the bones of her left lower extremity. While waiting for the definitive pathologic diagnosis of PMHE, denosumab, a human immunoglobulin G2 monoclonal antibody against RANKL, was initiated to treat progressive bone absorption after curettage of one of the lesions. Denosumab induced osteosclerosis around the lesions and pain relief and was discontinued 4 years after its initiation. Although all of the multifocal lesions remained, they all became less FDG-avid (SUVmax, 2.6), and the patient developed no signs of new lesions or distant metastasis. Conclusion: Denosumab plays a certain role in prevention of bone destruction by PMHE through suppression of osteoclast-like giant cells and would be an excellent treatment for bone absorption by PMHE of bone.

  • Frequent mutations of genes encoding vacuolar H <sup>+</sup> -ATPase components in granular cell tumors

    Sekimizu M., Yoshida A., Mitani S., Asano N., Hirata M., Kubo T., Yamazaki F., Sakamoto H., Kato M., Makise N., Mori T., Yamazaki N., Sekine S., Oda I., Watanabe S., Hiraga H., Yonemoto T., Kawamoto T., Naka N., Funauchi Y., Nishida Y., Honoki K., Kawano H., Tsuchiya H., Kunisada T., Matsuda K., Inagaki K., Kawai A., Ichikawa H.

    Genes Chromosomes and Cancer （Genes Chromosomes and Cancer)  58 （ 6 ） 373 - 380 2019.06

    ISSN  10452257

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    © 2018 Wiley Periodicals, Inc. Granular cell tumors (GCTs) are rare mesenchymal tumors that exhibit a characteristic morphology and a finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss-of-function mutations of ATP6AP1 and ATP6AP2 were described. Thus, we performed whole-exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples. From these genomic analyses, we identified mutations in genes encoding vacuolar H + -ATPase (V-ATPase) components, including ATP6AP1 and ATP6AP2, in 33 (65%) GCTs. ATP6AP1 and ATP6AP2 mutations were found in 23 (45%) and 2 (4%) samples, respectively, and all were truncating or splice site mutations. In addition, seven other genes encoding V-ATPase components were also mutated, and three mutations in ATP6V0C occurred on the same amino acid (isoleucine 136). These V-ATPase component gene mutations were mutually exclusive, with one exception. These results suggest that V-ATPase function is impaired in GCTs not only by loss-of-function mutations of ATP6AP1 and ATP6AP2 but also through mutations of other subunits. Our findings provide additional support for the hypothesis that V-ATPase dysfunction promotes GCT tumorigenesis.

  • Preservation of the Epiphysis and Growth Plate in the Surgical Management of Femoral Osteosarcoma in a Skeletally Immature Patient by Intercalary Resection and Biological Reconstruction: A Case Report

    Yoda Y., Yamaguchi S., Hirozane T., Asano N., Seki A., Morioka H., Nakayama R., Nakamura M., Matsumoto M.

    Case Reports in Oncology （Case Reports in Oncology)  12 （ 2 ） 513 - 522 2019.05

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    © 2019 The Author(s) Published by S. Karger AG, Basel. Osteosarcoma arises most frequently in the metaphysis around the knee and its management by limb salvage surgery in skeletally immature pediatric patients is extremely challenging. Common reconstructive methods such as endoprosthetic or biological reconstruction are not fully capable of dealing with durability-related and growth-related problems and their functional outcomes are not as good as those seen in adult cases. A definitive limb salvaging procedure in children that outperforms amputation or rotationplasty has not yet been established. Herein, we report a case of stage IV osteosarcoma in the femur of a 7-year-old boy that was safely managed with intercalary resection preserving the distal femoral growth plate and epiphysis, followed by biological reconstruction using a frozen tumor-devitalized autograft. Good response to preoperative chemotherapy and the diaphyseal location of the tumor enabled us to perform a tumor resection that spared the growth plate and preserved the native knee joint structure. Plate fixation over the growth plate was terminated by removing the locking screws in the epiphysis after 44 months, which restored growth capacity to some extent. At 50 months postoperatively, no recurrence or progression of the disease was observed. The patient uses an extension shoe and reports having little discomfort in his daily life despite having a restricted range of motion and limb length discrepancy. In conclusion, limb salvage with biological reconstruction in skeletally immature patients can provide an acceptable functional outcome, including minimized limb length discrepancy, if critical damage to the growth plate and articular components can be avoided.

  • Novel NTRK3 Fusions in Fibrosarcomas of Adults

    Yamazaki F., Nakatani F., Asano N., Wakai S., Sekimizu M., Mitani S., Kubo T., Kawai A., Ichikawa H., Yoshida A.

    American Journal of Surgical Pathology （American Journal of Surgical Pathology)  43 （ 4 ） 523 - 530 2019.04

    ISSN  01475185

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    © 2018 Wolters Kluwer Health, Inc. All rights reserved. NTRK fusions in malignant tumors are therapeutic targets of tyrosine kinase inhibitors. Because they occur only in a small subset of mesenchymal tumors, knowledge regarding the corresponding histology is important to effectively identify patients who could benefit from targeted therapy. In this study, using RNA sequencing, we identified novel NTRK3 fusions involving related partner genes in 2 adult bone and soft tissue tumors that met the current histologic criteria of fibrosarcoma. Case 1 involved the left radius of a 38-year-old woman, whereas in case 2, the right thigh of a 26-year-old man was affected. Histologically, both tumors consisted of the long fascicular growth of long spindle cells. The tumor in case 1 additionally showed focal myxoid changes. Tumor cells had nonpleomorphic, atypical nuclei, and lacked evidence of a specific line of differentiation. Both tumors showed widespread CD34 immunoreactivity and very limited expression of actin. RNA sequencing detected in-frame fusion transcripts of STRN (exon 3)-NTRK3 (exon 14) in case 1 and STRN3 (exon 3)-NTRK3 (exon 14) in case 2, which were confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. Pan-TRK immunostaining was diffusely positive in both cases. Fluorescence in situ hybridization showed signal patterns compatible with NTRK3 rearrangements in both cases, with case 2 additionally harboring a CDKN2A homozygous deletion. This study expands the clinicopathologic and genetic spectrum of sarcomas associated with NTRK fusions, and suggests that CD34-positive fibrosarcoma of bone and soft tissue could be a good candidate for NTRK testing.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Genomic and epigenomic analysis of dedifferentiated liposarcoma

    2021.04
    -
    2026.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • 脱分化型脂肪肉腫に対するエピゲノム解析

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, ORTHOPAEDICS

    2024

  • LECTURE SERIES, ORTHOPAEDICS

    2023

  • LECTURE SERIES, ORTHOPAEDICS

    2022

  • LECTURE SERIES, ORTHOPAEDICS

    2021

  • LECTURE SERIES, ORTHOPAEDICS

    2020

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