Okita, Hajime

写真a

Affiliation

School of Medicine, Division of Diagnostic Pathology (Shinanomachi)

Position

Associate Professor

External Links

Career 【 Display / hide

  • 2003.05
    -
    2010.03

    National Center for Child Health and Development, Department of Developmental Biology

  • 2010.04
    -
    2014.11

    National Center for Child Health and Development, Department of Pediatric Hematology and Oncology Research

  • 2014.12
    -
    Present

    Department of Pathology, Keio University School of Medicine

Academic Degrees 【 Display / hide

  • 博士(医学), 慶應義塾大学, Coursework

 

Research Areas 【 Display / hide

  • Human pathology

 

Papers 【 Display / hide

  • Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas

    Ichikawa D., Yamashita K., Okuno Y., Muramatsu H., Murakami N., Suzuki K., Kojima D., Kataoka S., Hamada M., Taniguchi R., Nishikawa E., Kawashima N., Narita A., Nishio N., Hama A., Kasai K., Mizuno S., Shimoyama Y., Nakaguro M., Okita H., Kojima S., Nakazawa A., Takahashi Y.

    npj Genomic Medicine (npj Genomic Medicine)  6 ( 1 )  2021.12

     View Summary

    Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.

  • Frequent breakpoints of focal deletion and uniparental disomy in 22q11.1 or 11.2 segmental duplication region reveal distinct tumorigenesis in rhabdoid tumor of the kidney

    Haruta M., Arai Y., Okita H., Tanaka Y., Takimoto T., Kamijo T., Oue T., Souzaki R., Taguchi T., Kuwahara Y., Chin M., Nakadate H., Hiyama E., Ishida Y., Koshinaga T., Kaneko Y.

    Genes Chromosomes and Cancer (Genes Chromosomes and Cancer)  60 ( 8 ) 546 - 558 2021.08

    ISSN  10452257

     View Summary

    SMARCB1 is mutated in most rhabdoid tumors (RTs) developing in the kidney (RTK) and various other organs. Focal deletions found in patients with 22q11.2 deletion syndrome show breakpoints within clusters of segmental duplications (SDs), and those in some RTs show breakpoints in the 22q11-q12 region. SDs are known to cause focal deletion mediated by non-allelic homologous recombination. The present study identified SMARCB1 alterations in all 30 RTKs, using SNP array CGH, MLPA, and sequence analyses. Twenty-eight tumors had a total of 51 breakpoints forming focal 22q deletion and/or uniparental disomy (22qUPD), and the other two had compound mutation with no breakpoints in 22q. Twenty-four (47.1%) of the 51 breakpoints were within SDs, and occurred in 16 (53.3%) of the 30 tumors. The association of breakpoints with SDs was found not only in focal deletion, but also in 22qUPD, indicating that SDs mediate the first and second hits (focal deletion) and the second hit (22qUPD) of SMARCB1 alteration. Of the 51 breakpoints, 14 were recurrent, and 10 of the 14 were within SDs, suggesting the presence of hotspots in the 22q11.2 region. One recurrent breakpoint outside SDs resided in SMARCB1, suggesting inactivation of the gene by out-of-frame fusion. The association between SDs and focal deletion has been reported in two other types of cancer. RTKs may be the third example of SD-associated tumors. Thus, the present study indicated that RTKs exploit genomic instability in the 22q11.1-11.2 SDs region, and 22qUPD caused by mitotic recombination may also be mediated by SDs.

  • Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group

    Umeda K., Miyamura T., Yamada K., Sano H., Hosono A., Sumi M., Okita H., Kumamoto T., Kawai A., Hirayama J., Jyoko R., Sawada A., Nakayama H., Hosoya Y., Maeda N., Yamamoto N., Imai C., Hasegawa D., Chin M., Ozaki T.

    Cancer Reports (Cancer Reports)  4 ( 3 )  2021.06

     View Summary

    Background: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. Aim: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. Methods and results: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P =.002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P =.006). Conclusions: The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT.

  • Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

    Nakamura K., Aimono E., Oba J., Hayashi H., Tanishima S., Hayashida T., Chiyoda T., Kosaka T., Hishida T., Kawakubo H., Kitago M., Okabayashi K., Funakoshi T., Okita H., Ikeda S., Takaishi H., Nishihara H.

    Medical Oncology (Medical Oncology)  38 ( 4 )  2021.04

    ISSN  13570560

     View Summary

    Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

  • Prognostic and therapeutic factors influencing the clinical outcome of metastatic Ewing sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group

    Umeda K., Miyamura T., Yamada K., Sano H., Hosono A., Sumi M., Okita H., Kamio T., Maeda N., Fujisaki H., Jyoko R., Watanabe A., Hosoya Y., Hasegawa D., Takenaka S., Nakagawa S., Chin M., Ozaki T.

    Pediatric Blood and Cancer (Pediatric Blood and Cancer)  68 ( 3 )  2021.03

    ISSN  15455009

     View Summary

    Background: The prognosis of patients with metastatic Ewing sarcoma family of tumors (ESFT) remains poor. Procedure: We retrospectively analyzed 57 patients diagnosed with metastatic ESFT between 2000 and 2018 to identify prognostic and therapeutic factors affecting the clinical outcome. Results: The 3-year overall survival (OS) rate of the entire cohort was 46.8% (95% confidence interval [CI], 33.0-59.4%). Treatment-related death was not observed. Multivariate analysis identified stem cell transplantation (SCT), response to first-line chemotherapy, and bone metastasis as independent risk factors for OS. Objective response rate to first-line chemotherapy was 65.1% in the 43 evaluable patients. There was no significant difference in the response to different types of first-line chemotherapy. Among patients with lung metastasis alone, the 3-year OS rate was higher in 13 patients who received local treatment than in four who did not, although the difference was not significant. Conclusions: One possible reason for the high OS rates was the absence of treatment-related mortality even in patients receiving SCT, which could be attributed to advances in the management of post-SCT complications. Novel first-line chemotherapy strategies need to be established to improve the disease status prior to SCT in a higher proportion of patients.

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

Presentations 【 Display / hide

  • Bcl-2関連遺伝子EATのトランスジェニック・マウスでは,多彩な腫瘍が発生する

    Ookita Hajime,Umezawa Akihiro,Matsushita Kenichi,Suzuki Atsushi,Shimoda Kouji,Fukuda Mariko,Sano Makoto,Yamada Taketo,Hata Junichi

    第90回日本病理学会総会, 2001.04

  • Bcl-2関連遺伝子EATのトランスジェニック・マウスでは多彩な腫瘍が発生する

    Ookita Hajime,Umezawa Akihiro,Matsushita Kenichi,Suzuki Jun,Shimoda Kouji,Fukuma Mariko,Sano Makoto,Yamada Taketo,Hata Junichi

    第59回日本癌学会総会, 2000.10

  • Molecular analysis of the Ewing family of tumors in japan:EWS/ETS fusion genes are availablefor diagnosis

    Okita H, Umezawa A, Urano F, Yabe H, Fukuma M, Hata J

    Interanational Congress of the international Academy of Pathology, 2000.10

  • Islet cells hyperplasia/Adenoma in the EAT transgenic mice

    Umezawa A, Matsusita K, Okita H, Suzuki A, Ando T, Shimoda K, Sano M, Fukuma M, Yamada T, Urano F, Hata J

    International Congress of the International Academy of Pathology, 2000.10

  • EAT/(Bcl-2関連遺伝子)トランスジェニック・マウスにおける膵ラ氏島の過形成及び腺腫

    Ookita Hajime,Umezawa Akihiro,Matsushita Kenichi,Suzuki Jun,Shimoda Kouji,Fukuma Mariko,Sano Makoto,Yamada Taketo,Hata Junichi

    第89回日本病理学会, 2000.04

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

  • エピゲノム修飾因子の機能解析による小児固形腫瘍の発症機構解明

    2016.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大喜多 肇, Grant-in-Aid for Scientific Research (C), Principal Investigator

 

Courses Taught 【 Display / hide

  • GENERAL PATHOLOGY

    2021

  • DISEASES OF ORGAN SYSTEMS

    2021

  • DIAGNOSTIC PATHOLOGY

    2021

  • GENERAL PATHOLOGY

    2020

  • DISEASES OF ORGAN SYSTEMS

    2020

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