Details of the Researcher

PHOTO

Yasunobu Okamura
Section
Advanced Research Center for Innovations in Next-Generation Medicine
Job title
Senior Assistant Professor
Degree

Research History 1

  • 2018/04 - Present
    Tohoku University　Advanced Research Center for Innovations in Next-Generation Medicine　Assitant Professor

Education 1

  • Tohoku University　Graduate School of Information Sciences　Applied Information Science

    2011/04 - 2016/03

Research Interests 1

  • Bioinformatics

Research Areas 1

  • Informatics / Biological, health, and medical informatics /

Papers 42

  1. BCL11B enhancer hijacking by t(14;16)(q32;q24) translocation defines a novel high-risk subtype of T-ALL. International-journal

    Kaito Mimura, Akira Kaino, Yotaro Ochi, Yu-Hsuan Chang, Masafumi Seki, June Takeda, Saori Katayama, Hidetaka Niizuma, Yoji Sasahara, Yoko Mizoguchi, Maiko Shimomura, Ryosuke Koyamada, Rintaro Ono, Daisuke Hasegawa, Kazuki Mitani, Hirohito Kubota, Satoshi Yoshihara, Nobuhiro Hiramoto, Akihito Otsuki, Yasunobu Okamura, Fumiki Katsuoka, Kengo Kinoshita, Masataka Hasegawa, Marina Togo-Ohno, Hirona Maeda, Nobuyuki Kakiuchi, Mai Takeuchi, Aiko Sato-Otsubo, Shota Kato, Kentaro Watanabe, Kotoe Katayama, Seiya Imoto, Yuichi Shiraishi, Katsuyoshi Koh, Souichi Suenobu, Eiso Hiyama, Susumu Goyama, Atsuo Kikuchi, Seishi Ogawa, Motohiro Kato, Yasuhito Nannya, Junko Takita, Kenichi Yoshida

    Blood　2026/03/05

    DOI： 10.1182/blood.2025031466 　

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    The molecular classification of T-cell acute lymphoblastic leukemia (T-ALL) remains incomplete, limiting risk stratification and the development of targeted therapies. Enhancer hijacking is a critical oncogenic mechanism that deregulates proto-oncogenes by repositioning cis-regulatory regions via structural variants. Here, we performed an integrated analysis of pediatric and adult T-ALL and mixed phenotype acute leukemias (MPALs), using whole-genome and whole-transcriptome sequencing. This analysis identified a group of 14 patients with predominantly T-lineage neoplasms driven by a t(14;16)(q32;q24) translocation, harboring universal GATA3 mutations and CDKN2A/B deletions. Mechanistically, this translocation repositions the ThymoD locus downstream of BCL11B, causing monoallelic, ectopic overexpression of FENDRR and mesenchymal transcription factor genes FOXF1 and FOXC2, activating epithelial-mesenchymal transition (EMT) transcription signatures. Immunophenotypic and single-cell RNA-seq analyses revealed marked lineage ambiguity with myeloid and B-cell differentiation potentials specific to this subtype. Furthermore, functional analyses in CD34-positive cord blood cells demonstrated that FOXF1 overexpression promotes myeloid differentiation while suppressing T-cell differentiation, serving as a key factor for lineage specification. Clinically, this subtype was detected in 0.15-4.0% of T-ALL/MPAL cases depending on the cohort, showing a median age of 15 years and enrichment in adolescents and young adults (AYA). Importantly, patients with t(14;16)(q32;q24) have an extremely poor prognosis, showing a trend toward worse outcomes than high-risk groups such as KMT2A-rearranged early T-cell progenitor (ETP)-like, SPI1-rearranged, and LMO2 γδ-like T-ALLs. The unique molecular landscape and poor prognosis of patients with the t(14;16)(q32;q24) translocation underscore the need for the development of novel subtype-specific therapeutic approaches.

  2. Advancements in Whole-Genome Sequencing Protocols: A Decade of In-House Operations and Quality Controls at the Tohoku Medical Megabank.

    Fumiki Katsuoka, Junko Kawashima, Shu Tadaka, Akihito Otsuki, Yasunobu Okamura, Takafumi Suzuki, Takanori Hidaka, Kazuki Kumada, Fuji Nagami, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto

    JMA journal　8　(4)　1039-1052　2025/10/15

    DOI： 10.31662/jmaj.2025-0159 　

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    Population-scale human whole-genome sequencing (WGS) projects are ongoing worldwide. At a time when such large-scale genome projects were uncommon, the Tohoku Medical Megabank Project initiated genome analysis of the general population in Japan, aiming to build a foundation for personalized medicine and prevention. Recently, we have completed the WGS of 100,000 participants, and research utilizing this genomic foundation is in progress. Early in the project, we realized that standard protocols were not always suitable for large-scale sequencing, necessitating the development of optimized operations and quality control methods. To accommodate various sequencing platforms and adapt protocols to the scale of analysis, we have continuously refined our methods. As multiplex sequencing analysis became standard, we aimed to ensure uniform data quantity across samples. With the advent of large-scale analyses, streamlining operations has also been a critical focus. In this paper, we share the details of our WGS operations and quality control methods developed over a decade, highlighting the unique methods and know-how we have established.

  3. JG2: an updated version of the Japanese population-specific reference genome

    Sirawit Sriwichaiin, Satoshi Makino, Takamitsu Funayama, Akihito Otsuki, Junko Kawashima, Yasunobu Okamura, Shu Tadaka, Fumiki Katsuoka, Kazuki Kumada, Shuichi Tsutsumi, Kengo Kinoshita, Masayuki Yamamoto, Gen Tamiya, Jun Takayama

    Human Genome Variation　12　(1)　2025/10/01

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41439-025-00326-y 　

    eISSN： 2054-345X

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    Abstract Here we present the construction of JG2, an updated population-specific reference genome for the Japanese population. Utilizing data from three individuals previously used in the construction of JG1, several methodologies were employed to enhance genomic coverage and assembly quality. Hi-C sequencing technology facilitated phase-aware assembly, generating two haploid assemblies per individual and enabling improved representation of genetic variation. A meta-assembly strategy and a majority decision approach further refined assembly quality by combining the best sequences from multiple assemblies and minimizing the inclusion of rare variants. The resulting JG2 genome comprises chromosome-level sequences, mitochondrial chromosomes and unplaced scaffolds, offering more comprehensive coverage of the Japanese genome. Comparative analyses with other reference genomes demonstrated the accuracy and representativeness of JG2, highlighting its utility for genetic research involving the Japanese population. Overall, by adopting the phased assembly technique, JG2 represents a substantial advancement over the collapsed assembly-based JG1, with improvements including a greater number of identified variants (3,115,695 variants, of which 298,644 had an allele frequency (AF) of 1.0 in the 3.5KJPNv2 AF panel) and a higher N50 value (152,668,378 bp). These enhancements provide researchers with a more precise and comprehensive resource for understanding the genetic landscape of the Japanese population. The sequences and annotations are available on the jMorp website (https://jmorp.megabank.tohoku.ac.jp/).

  4. Sequential Plasma Metabolome and Proteome Analyses to Develop a Novel Monitoring Strategy for Patients with Epithelial Ovarian Cancer: A Pilot Study

    Eiji Hishinuma, Shogo Shigeta, Naomi Matsukawa, Yasunobu Okamura, Ikuko N. Motoike, Takamichi Minato, Yusuke Shibuya, Jun Yasuda, Kengo Kinoshita, Seizo Koshiba, Muneaki Shimada

    International Journal of Molecular Sciences　26　(12)　5435-5435　2025/06/06

    Publisher: MDPI AG

    DOI： 10.3390/ijms26125435 　

    eISSN： 1422-0067

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    Epithelial ovarian cancer (EOC) is diagnosed at an advanced stage in over half of the patients and its prognosis remains unfavorable. CA125, one of the most frequent positive tumor markers in patients with EOC, has certain limitations. Therefore, more accurate clinical biomarkers are needed. Liquid biopsy with cancer related molecules, such as circulating tumor DNA, is a new option for cancer diagnosis and prognosis. We explored the potential of plasma metabolomic and proteomic analyses as novel monitoring methods for the patients with EOC. Of seven patients, six experienced disease recurrence or progression. CA125 plasma measurements were conducted for disease monitoring. Plasma metabolome and proteome analyses were performed using liquid chromatography–tandem mass spectrometry. Ten and four metabolome indicators were significantly increased and decreased in association with chemotherapeutic resistance, respectively. In addition, thirty-seven and nine proteins displayed high and low levels associated with chemotherapeutic resistance, respectively. Several metabolome pathways and protein concentrations corresponded to the clinical course of each patient. This pilot study suggested the potential of the assessment of metabolome and proteome analysis as a useful tool for developing novel monitoring biomarkers for patients with recurrent EOC.

  5. Quantum Key Distribution Network and Quantum Secure Cloud Technologies for Genome Medicine Use Cases

    Yoshimichi Tanizawa, Akira Murakami, Ririka Takahashi, Kazuaki Doi, Mamiko Kujiraoka, Hideaki Sato, Muneaki Shimada, Nobuo Yaegashi, Shogo Shigeta, Yasunobu Okamura, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Fuji Nagami, Masayuki Yamamoto, Mikio Fujiwara

    IEEE Transactions on Quantum Engineering　6　1-15　2025

    Publisher: Institute of Electrical and Electronics Engineers (IEEE)

    DOI： 10.1109/tqe.2025.3611335 　

    eISSN： 2689-1808

  6. Next-generation sequencing analysis with a population-specific human reference genome.

    Tomohisa Suzuki, Kota Ninomiya, Takamitsu Funayama, Yasunobu Okamura, Shu Tadaka, Kengo Kinoshita, Masayuki Yamamoto, Shigeo Kure, Atsuo Kikuchi, Gen Tamiya, Jun Takayama

    Genes & genetic systems　2024/10/28

    DOI： 10.1266/ggs.24-00112 　

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    Next-generation sequencing (NGS) has become widely available and is routinely used in basic research and clinical practice. The reference genome sequence is an essential resource for NGS analysis, and several population-specific reference genomes have recently been constructed to provide a choice to deal with the vast genetic diversity of human samples. However, resources supporting population-specific references are insufficient, and it is burdensome to perform analysis using these reference genomes. Here, we constructed a set of resources to support NGS analysis using the Japanese reference genome, JG. We created resources for variant calling, variant-effect prediction, gene and repeat element annotations, read mappability, and RNA-seq analysis. We also provide a resource for reference coordinate conversion for further annotation enrichment. We then provide a variant calling protocol with JG. Our resources provide a guide to prepare sufficient resources for the use of population-specific reference genomes and can facilitate the migration of reference genomes.

  7. Two-stage strategy using denoising autoencoders for robust reference-free genotype imputation with missing input genotypes

    Kaname Kojima, Shu Tadaka, Yasunobu Okamura, Kengo Kinoshita

    Journal of Human Genetics　69　(10)　511-518　2024/06/25

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s10038-024-01261-6 　

    ISSN： 1434-5161

    eISSN： 1435-232X

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    Abstract Widely used genotype imputation methods are based on the Li and Stephens model, which assumes that new haplotypes can be represented by modifying existing haplotypes in a reference panel through mutations and recombinations. These methods use genotypes from SNP arrays as inputs to estimate haplotypes that align with the input genotypes by analyzing recombination patterns within a reference panel, and then infer unobserved variants. While these methods require reference panels in an identifiable form, their public use is limited due to privacy and consent concerns. One strategy to overcome these limitations is to use de-identified haplotype information, such as summary statistics or model parameters. Advances in deep learning (DL) offer the potential to develop imputation methods that use haplotype information in a reference-free manner by handling it as model parameters, while maintaining comparable imputation accuracy to methods based on the Li and Stephens model. Here, we provide a brief introduction to DL-based reference-free genotype imputation methods, including RNN-IMP, developed by our research group. We then evaluate the performance of RNN-IMP against widely-used Li and Stephens model-based imputation methods in terms of accuracy (R2), using the 1000 Genomes Project Phase 3 dataset and corresponding simulated Omni2.5 SNP genotype data. Although RNN-IMP is sensitive to missing values in input genotypes, we propose a two-stage imputation strategy: missing genotypes are first imputed using denoising autoencoders; RNN-IMP then processes these imputed genotypes. This approach restores the imputation accuracy that is degraded by missing values, enhancing the practical use of RNN-IMP.

  8. Molecular pathological demonstration of an unusual angiosarcoma-like dedifferentiation pattern in hepatocellular carcinoma. International-journal

    Keigo Murakami, Taito Itoh, Yasunobu Okamura, Kengo Kinoshita, Hideki Ota, Michiaki Unno, Takashi Kamei, Toru Furukawa

    Pathology international　74　(3)　157-159　2024/02/06

    DOI： 10.1111/pin.13412 　

  9. 患者由来膵癌オルガノイドの樹立と解析(Establishment and Characterization of Patient-derived Pancreatic Cancer Organoids)

    高橋 利真, 椎原 正尋, 吉田 拓矢, 石川 智彦, 村上 圭吾, 岡村 容伸, 木下 賢吾, 海野 倫明, 元井 冬彦, 古川 徹

    日本病理学会会誌　113　(1)　402-402　2024/02

    Publisher: (一社)日本病理学会

    ISSN： 0300-9181

  10. Next-generation sequencing analysis with a population-specific human reference genome

    Tomohisa Suzuki, Kota Ninomiya, Takamitsu Funayama, Yasunobu Okamura, Shu Tadaka, Kengo Kinoshita, Masayuki Yamamoto, Shigeo Kure, Atsuo Kikuchi, Gen Tamiya, Jun Takayama

    Genes & Genetic Systems　2024

    Publisher: Genetics Society of Japan

    DOI： 10.1266/ggs.24-00112 　

    ISSN： 1341-7568

    eISSN： 1880-5779

  11. jMorp: Japanese Multi-Omics Reference Panel update report 2023. International-journal

    Shu Tadaka, Junko Kawashima, Eiji Hishinuma, Sakae Saito, Yasunobu Okamura, Akihito Otsuki, Kaname Kojima, Shohei Komaki, Yuichi Aoki, Takanari Kanno, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Jun Takayama, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Ritsuko Shimizu, Masahiro Hiratsuka, Ikuko N Motoike, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research　2023/11/01

    DOI： 10.1093/nar/gkad978 　

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    Modern medicine is increasingly focused on personalized medicine, and multi-omics data is crucial in understanding biological phenomena and disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing disease risk and drug response. Therefore, multi-omics data from specific ethnic populations are essential for the effective implementation of personalized medicine. Various prospective cohort studies, such as the UK Biobank, All of Us and Lifelines, have been conducted worldwide. The Tohoku Medical Megabank project was initiated after the Great East Japan Earthquake in 2011. It collects biological specimens and conducts genome and omics analyses to build a basis for personalized medicine. Summary statistical data from these analyses are available in the jMorp web database (https://jmorp.megabank.tohoku.ac.jp), which provides a multidimensional approach to the diversity of the Japanese population. jMorp was launched in 2015 as a public database for plasma metabolome and proteome analyses and has been continuously updated. The current update will significantly expand the scale of the data (metabolome, genome, transcriptome, and metagenome). In addition, the user interface and backend server implementations were rewritten to improve the connectivity between the items stored in jMorp. This paper provides an overview of the new version of the jMorp.

  12. Gene rearrangement and expression of PRKACA and PRKACB governs morpho-biology of pancreatobiliary oncocytic neoplasms

    Taito Itoh, Yuko Omori, Mitsuru Seino, Katsuya Hirose, Fumiko Date, Yusuke Ono, Yusuke Mizukami, Shuichi Aoki, Masaharu Ishida, Masamichi Mizuma, Takanori Morikawa, Ryota Higuchi, Goro Honda, Yasunobu Okamura, Kengo Kinoshita, Michiaki Unno, Toru Furukawa

    Modern Pathology　100358-100358　2023/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.modpat.2023.100358 　

    ISSN： 0893-3952

  13. Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials. International-journal Peer-reviewed

    Tomohiko Ishikawa, Takenori Ogawa, Masahiro Shiihara, Hajime Usubuchi, Yuko Omori, Katsuya Hirose, Taito Itoh, Takuya Yoshida, Ayako Nakanome, Akira Okoshi, Kenjiro Higashi, Ryo Ishii, Masahiro Rokugo, Shun Wakamori, Yasunobu Okamura, Kengo Kinoshita, Yukio Katori, Toru Furukawa

    iScience　26　(5)　106695-106695　2023/05/19

    DOI： 10.1016/j.isci.2023.106695 　

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    Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

  14. Morphometric analysis of nuclear shape irregularity as a novel predictor of programmed death-ligand 1 expression in lung squamous cell carcinoma. International-journal

    Ryoko Saito-Koyama, Keiichi Tamai, Jun Yasuda, Yasunobu Okamura, Yuto Yamazaki, Chihiro Inoue, Yasuhiro Miki, Jiro Abe, Hisashi Oishi, Ikuro Sato, Hironobu Sasano

    Virchows Archiv : an international journal of pathology　2023/05/12

    DOI： 10.1007/s00428-023-03548-z 　

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    Immune checkpoint inhibitor (ICI) therapy has been established as one of the key treatment strategies for lung squamous cell carcinoma (LUSQ). The status of programmed death-ligand 1 (PD-L1) in tumor cells and/or immune cells using immunohistochemistry has been primarily used as a surrogate marker for determining ICI treatment; however, when the tissues to be examined are small, false-negative results could be unavoidable due to the heterogeneity of PD-L1 immunoreactivity. To overcome this practical limitation, we attempted to explore the status of nuclear atypia evaluated using morphometry as a potential predictor of PD-L1 status in LUSQ. We correlated the parameters related to nuclear atypia with PD-L1 status using two different cohorts of LUSQ patients (95 cases from The Cancer Genome Atlas database and 30 cases from the Miyagi Cancer Center). Furthermore, we studied the gene mutation status to elucidate the genetic profile of PD-L1 predictable cases. The results revealed that nuclear atypia, especially morphometric parameters related to nuclear shape irregularity, including aspect ratio, circularity, roundness, and solidity, were all significantly associated with PD-L1 status. Additionally, LUSQ cases with high PD-L1 expression and pronounced nuclear atypia were significantly associated with C10orf71 and COL14A1 mutations compared with those with low PD-L1 expression and mild nuclear atypia. We demonstrated for the first time that nuclear shape irregularity could represent a novel predictor of PD-L1 expression in LUSQ. Including the morphometric parameters related to nuclear atypia in conjunction with PD-L1 status could help determine an effective ICI therapeutic strategy; however, further investigation is required.

  15. Plasma metabolic disturbances during pregnancy and postpartum in women with depression. International-journal Peer-reviewed

    Zhiqian Yu, Naomi Matsukawa, Daisuke Saigusa, Ikuko N Motoike, Chiaki Ono, Yasunobu Okamura, Tomomi Onuma, Yuta Takahashi, Mai Sakai, Hisaaki Kudo, Taku Obara, Keiko Murakami, Matusyuki Shirota, Saya Kikuchi, Natsuko Kobayashi, Yoshie Kikuchi, Junichi Sugawara, Naoko Minegishi, Soichi Ogishima, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Shinichi Kuriyama, Seizo Koshiba, Hiroaki Tomita

    iScience　25　(12)　105666-105666　2022/12/22

    DOI： 10.1016/j.isci.2022.105666 　

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    Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

  16. jMorp: Japanese Multi Omics Reference Panel

    田高 周, 菱沼 英史, 井上 仁, 青木 裕一, 岡村 容伸, 川嶋 順子, 大槻 晃史, 田口 恵子, 菅野 貴成, 元池 育子, 勝岡 史城, 小柴 生造, 木下 賢吾

    トーゴーの日2022　1　2022/10/05

    Publisher: JST NBDC事業推進部

    DOI： 10.18908/togo2022.p040 　

  17. Construction of a trio-based structural variation panel utilizing activated T lymphocytes and long-read sequencing technology. International-journal

    Akihito Otsuki, Yasunobu Okamura, Noriko Ishida, Shu Tadaka, Jun Takayama, Kazuki Kumada, Junko Kawashima, Keiko Taguchi, Naoko Minegishi, Shinichi Kuriyama, Gen Tamiya, Kengo Kinoshita, Fumiki Katsuoka, Masayuki Yamamoto

    Communications biology　5　(1)　991-991　2022/09/20

    DOI： 10.1038/s42003-022-03953-1 　

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    Long-read sequencing technology enable better characterization of structural variants (SVs). To adapt the technology to population-scale analyses, one critical issue is to obtain sufficient amount of high-molecular-weight genomic DNA. Here, we propose utilizing activated T lymphocytes, which can be established efficiently in a biobank to stably supply high-grade genomic DNA sufficiently. We conducted nanopore sequencing of 333 individuals constituting 111 trios with high-coverage long-read sequencing data (depth 22.2x, N50 of 25.8 kb) and identified 74,201 SVs. Our trio-based analysis revealed that more than 95% of the SVs were concordant with Mendelian inheritance. We also identified SVs associated with clinical phenotypes, all of which appear to be stably transmitted from parents to offspring. Our data provide a catalog of SVs in the general Japanese population, and the applied approach using the activated T-lymphocyte resource will contribute to biobank-based human genetic studies focusing on SVs at the population scale.

  18. X chromosome aneuploidies and schizophrenia: association analysis and phenotypic characterization

    Itaru Kushima, Branko Aleksic, Hiroki Kimura, Masahiro Nakatochi, Tzuyao Lo, Masashi Ikeda, Makoto Arai, Ryota Hashimoto, Shusuke Numata, Yasunobu Okamura, Taku Obara, Toshiya Inada, Norio Ozaki

    Psychiatry and Clinical Neurosciences　2022/09/08

    Publisher: Wiley

    DOI： 10.1111/pcn.13474 　

    ISSN： 1323-1316

    eISSN： 1440-1819

  19. 患者由来がんオルガノイドの増殖と粘液分泌の特徴からみたIPMNの浸潤性表現型の立証(Characteristics of growth and mucus secretion of patient-derived organoids may substantiate invasive phenotypes of IPMN)

    Shiihara Masahiro, Ishikawa Tomohiko, Yoshida Takuya, Omori Yuko, Hirose Katsuya, Morikawa Takanori, Nakagawa Kei, Mizuma Masamichi, Otsuka Hideo, Motoi Fuyuhiko, Unno Michiaki, Okamura Yasunobu, Kinoshita Kengo, Furukawa Toru

    膵臓　37　(3)　A391-A392　2022/09

    Publisher: (一社)日本膵臓学会

    ISSN： 0913-0071

    eISSN： 1881-2805

  20. The association between ERK inhibitor sensitivity and molecular characteristics in colorectal cancer. International-journal

    Hodaka Tayama, Hideaki Karasawa, Akihiro Yamamura, Yasunobu Okamura, Fumiki Katsuoka, Hideyuki Suzuki, Taiki Kajiwara, Minoru Kobayashi, Yuuri Hatsuzawa, Masahiro Shiihara, Li Bin, Md Yeashin Gazi, Mizuki Sato, Kazuki Kumada, Shigehiro Ito, Muneaki Shimada, Toru Furukawa, Takashi Kamei, Shinobu Ohnuma, Michiaki Unno

    Biochemical and biophysical research communications　560　59-65　2021/06/30

    DOI： 10.1016/j.bbrc.2021.04.130 　

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    The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.

  21. Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers

    Masahiro Shiihara, Tomohiko Ishikawa, Yuriko Saiki, Yuko Omori, Katsuya Hirose, Shinichi Fukushige, Naoki Ikari, Ryota Higuchi, Masakazu Yamamoto, Takanori Morikawa, Kei Nakagawa, Hiroki Hayashi, Masamichi Mizuma, Hideo Ohtsuka, Fuyuhiko Motoi, Michiaki Unno, Yasunobu Okamura, Kengo Kinoshita, Toru Furukawa

    European Journal of Cancer　148　239-250　2021/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.ejca.2021.01.047 　

    ISSN： 0959-8049

  22. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. International-journal

    Shu Tadaka, Eiji Hishinuma, Shohei Komaki, Ikuko N Motoike, Junko Kawashima, Daisuke Saigusa, Jin Inoue, Jun Takayama, Yasunobu Okamura, Yuichi Aoki, Matsuyuki Shirota, Akihito Otsuki, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research　49　(D1)　D536-D544　2021/01/08

    DOI： 10.1093/nar/gkaa1034 　

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    In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. At that time, jMorp mainly consisted of metabolome data; however, now genome, methylome, and transcriptome data have been integrated in addition to the enhancement of the number of samples for the metabolome data. For genomic data, jMorp provides a Japanese reference sequence obtained using de novo assembly of sequences from three Japanese individuals and allele frequencies obtained using whole-genome sequencing of 8,380 Japanese individuals. In addition, the omics data include methylome and transcriptome data from ∼300 samples and distribution of concentrations of more than 755 metabolites obtained using high-throughput nuclear magnetic resonance and high-sensitivity mass spectrometry. In summary, jMorp now provides four different kinds of omics data (genome, methylome, transcriptome, and metabolome), with a user-friendly web interface. This will be a useful scientific data resource on the general population for the discovery of disease biomarkers and personalized disease prevention and early diagnosis.

  23. Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland

    Tomohiko Ishikawa, Takenori Ogawa, Ayako Nakanome, Yasunari Yamauchi, Hajime Usubuchi, Masahiro Shiihara, Takuya Yoshida, Yasunobu Okamura, Kengo Kinoshita, Yukio Katori, Toru Furukawa

    Virchows Archiv　2021/01/07

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00428-020-02981-8 　

    ISSN： 0945-6317

    eISSN： 1432-2307

  24. Identification of dominant transcripts in oxidative stress response by a full-length transcriptome analysis

    Akihito Otsuki, Yasunobu Okamura, Yuichi Aoki, Noriko Ishida, Kazuki Kumada, Naoko Minegishi, Fumiki Katsuoka, Kengo Kinoshita, Masayuki Yamamoto

    Molecular and Cellular Biology　2020/11/09

    Publisher: American Society for Microbiology

    DOI： 10.1128/mcb.00472-20 　

    ISSN： 0270-7306

    eISSN： 1098-5549

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    Our body responds to environmental stress by changing the expression levels of a series of cytoprotective enzymes/proteins through multilayered regulatory mechanisms, including the KEAP1-NRF2 system. While NRF2 upregulates the expression of many cytoprotective genes, there are fundamental limitations in short-read RNA sequencing (RNA-Seq), resulting in confusion regarding interpreting the effectiveness of cytoprotective gene induction at transcript level. To precisely delineate isoform usage in the stress response, we conducted independent full-length transcriptome profiling (isoform sequencing; Iso-Seq) analyses of lymphoblastoid cells from three volunteers under normal and electrophilic stress-induced conditions. We first determined the first exon usage in <italic>KEAP1</italic> and <italic>NFE2L2</italic> (encoding NRF2) and found the presence of transcript diversity. We then examined changes in isoform usage of NRF2 target genes under stress conditions and identified a few isoforms dominantly expressed in the majority of NRF2 target genes. The expression levels of isoforms determined by Iso-Seq analyses showed striking differences from those determined by short-read RNA-Seq; the latter could be misleading in regards to the abundance of transcripts. These results support that transcript usage is tightly regulated to produce functional proteins under electrophilic stress. Our present study strongly argues that there are important benefits that can be achieved by long-read transcriptome sequencing.

  25. Construction and Integration of Three De Novo Japanese Human Genome Assemblies toward a Population-Specific Reference Peer-reviewed

    Jun Takayama, Shu Tadaka, Kenji Yano, Fumiki Katsuoka, Chinatsu Gocho, Takamitsu Funayama, Satoshi Makino, Yasunobu Okamura, Atsuo Kikuchi, Junko Kawashima, Akihito Otsuki, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto, Gen Tamiya

    2019/12/02

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/861658 　

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    <title>ABSTRACT</title>The complete sequence of the human genome is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the international human reference genome (e.g., GRCh37), especially Asian populations, due to a strong bias toward European and African ancestries in a single mosaic haploid genome consisting chiefly of a single donor. Here, we performed <italic>de novo</italic> assembly of the genomes from three Japanese male individuals using &gt;100× PacBio long reads and Bionano optical maps per sample. We integrated the genomes using the major allele for consensus, and anchored the scaffolds using sequence-tagged site markers from conventional genetic and radiation hybrid maps to reconstruct each chromosome sequence. The resulting genome sequence, designated JG1, is highly contiguous, accurate, and carries the major allele in the majority of single nucleotide variant sites for a Japanese population. We adopted JG1 as the reference for confirmatory exome re-analyses of seven Japanese families with rare diseases and found that re-analysis using JG1 reduced false-positive variant calls versus GRCh37 while retaining disease-causing variants. These results suggest that integrating multiple genome assemblies from a single ethnic population can aid next-generation sequencing analyses of individuals originated from the population.

  26. A 12-kb structural variation in progressive myoclonic epilepsy was newly identified by long-read whole-genome sequencing International-journal Peer-reviewed

    Mizuguchi Takeshi, Suzuki Takeshi, Abe Chihiro, Umemura Ayako, Tokunaga Katsushi, Kawai Yosuke, Nakamura Minoru, Nagasaki Masao, Kinoshita Kengo, Okamura Yasunobu, Miyatake Satoko, Miyake Noriko, Matsumoto Naomichi

    JOURNAL OF HUMAN GENETICS　64　(5)　359-368　2019/05

    DOI： 10.1038/s10038-019-0569-5 　

    ISSN： 1434-5161

  27. Genomic testing for pancreatic cancer in clinical practice as real-world evidence. International-journal Peer-reviewed

    Hideyuki Hayashi, Shigeki Tanishima, Kyoko Fujii, Ryo Mori, Yasunobu Okamura, Emmy Yanagita, Ryosuke Matsuoka, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Dosaka-Akita, Hiroshi Nishihara

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]　18　(6)　647-654　2018/09

    DOI： 10.1016/j.pan.2018.07.006 　

    ISSN： 1424-3903

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    BACKGROUND: Precision medicine guided by comprehensive genome sequencing represents a potential treatment strategy for pancreatic cancer. However, clinical sequencing for pancreatic cancer entails several practical difficulties. We have launched an in-house clinical sequencing system and started genomic testing for patients with cancer in clinical practice. We have analyzed the clinical utility of this system in pancreatic cancer. METHODS: We retrospectively reviewed 20 patients with pancreatic cancer who visited our division. Genomic DNA was extracted from both tumor tissue and peripheral blood mononuclear cells obtained from the patients. We performed a comprehensive genomic testing using targeted amplicon sequencing for 160 cancer-related genes. The primary endpoints were the detection rates of potential actionable and druggable gene alterations. The secondary endpoints were the detection rate of secondary germline findings, the rate of re-biopsy required for genome sequencing, survival time after the initial visit (post-sequencing survival time), and turnaround time. RESULTS: Although re-biopsy was required for 25% (5/20) of all patients, genomic testing was performed in all patients. Actionable and druggable gene alterations were detected in 100% (20/20) and 35% (7/20) of patients, respectively, whereas secondary germline findings were detected in 5% (1/20) of patients. The median turnaround times for physicians and patients were 20 and 26 days, respectively. The median post-sequencing survival time was 10.3 months. Only 10% (2/20) of all patients were treated with therapeutic agents based on the outcomes of genomic testing. CONCLUSIONS: The clinical application of comprehensive genomic testing for pancreatic cancer was feasible and promising in clinical practice.

  28. Matataki: an ultrafast mRNA quantification method for large-scale reanalysis of RNA-Seq data. Peer-reviewed

    Okamura Y, Kinoshita K

    BMC bioinformatics　19　(1)　266　2018/07

    DOI： 10.1186/s12859-018-2279-y 　

  29. Zinc finger-IRF composite elements bound by Ikaros/IRF4 complexes function as gene repression in plasma cell. Peer-reviewed

    Ochiai K, Kondo H, Okamura Y, Shima H, Kurokochi Y, Kimura K, Funayama R, Nagashima T, Nakayama K, Yui K, Kinoshita K, Igarashi K

    Blood advances　2　(8)　883-894　2018/04

    DOI： 10.1182/bloodadvances.2017010413 　

    ISSN： 2473-9529

  30. Clinical implementation of a comprehensive targeted amplicon sequencing system for the patients with gastrointestinal cancer as a real world evidence in Japan. Peer-reviewed

    Hayashi Hideyuki, Tanishima Shigeki, Mori Ryo, Okamura Yasunobu, Yanagita Emmy, Matsuoka Ryosuke

    JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018/02/01

    ISSN： 0732-183X

  31. Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis Peer-reviewed

    Risa Ebina-Shibuya, Mitsuyo Matsumoto, Makoto Kuwahara, Kyoung-Jin Jang, Manabu Sugai, Yoshiaki Ito, Ryo Funayama, Keiko Nakayama, Yuki Sato, Naoto Ishii, Yasunobu Okamura, Kengo Kinoshita, Kohei Kometani, Tomohiro Kurosaki, Akihiko Muto, Masakazu Ichinose, Masakatsu Yamashita, Kazuhiko Igarashi

    JOURNAL OF BIOLOGICAL CHEMISTRY　292　(44)　18098-18112　2017/11

    DOI： 10.1074/jbc.M117.808535 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  32. Establishment of Protocols for Global Metabolomics by LC-MS for Biomarker Discovery Peer-reviewed

    Daisuke Saigusa, Yasunobu Okamura, Ikuko N. Motoike, Yasutake Katoh, Yasuhiro Kurosawa, Reina Saijyo, Seizo Koshiba, Jun Yasuda, Hozumi Motohashi, Junichi Sugawara, Osamu Tanabe, Kengo Kinoshita, Masayuki Yamamoto

    PLOS ONE　11　(8)　e0160555　2016/08

    DOI： 10.1371/journal.pone.0160555 　

    ISSN： 1932-6203

  33. ATTED-II in 2016: A Plant Coexpression Database Towards Lineage-Specific Coexpression Peer-reviewed

    Yuichi Aoki, Yasunobu Okamura, Shu Tadaka, Kengo Kinoshita, Takeshi Obayashi

    PLANT AND CELL PHYSIOLOGY　57　(1)　e5　2016/01

    DOI： 10.1093/pcp/pcv165 　

    ISSN： 0032-0781

    eISSN： 1471-9053

  34. ALCOdb: Gene Coexpression Database for Microalgae Peer-reviewed

    Yuichi Aoki, Yasunobu Okamura, Hiroyuki Ohta, Kengo Kinoshita, Takeshi Obayashi

    PLANT AND CELL PHYSIOLOGY　57　(1)　e3　2016/01

    DOI： 10.1093/pcp/pcv190 　

    ISSN： 0032-0781

    eISSN： 1471-9053

  35. 転写因子による細胞分化・増殖抑制 転写因子IRF4が支配する胚中心B細胞および形質細胞分化誘導の遺伝子発現ネットワーク

    落合 恭子, 近藤 晴香, 岡村 容伸, 木下 賢吾, 五十嵐 和彦

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[2W9-6]　2015/12

    Publisher: (公社)日本生化学会

  36. Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules Peer-reviewed

    Yasunobu Okamura, Takeshi Obayashi, Kengo Kinoshita

    PLOS ONE　10　(7)　e0132039　2015/07

    DOI： 10.1371/journal.pone.0132039 　

    ISSN： 1932-6203

  37. COXPRESdb in 2015: coexpression database for animal species by DNA-microarray and RNAseq-based expression data with multiple quality assessment systems Peer-reviewed

    Yasunobu Okamura, Yuichi Aoki, Takeshi Obayashi, Shu Tadaka, Satoshi Ito, Takafumi Narise, Kengo Kinoshita

    NUCLEIC ACIDS RESEARCH　43　(D1)　D82-D86　2015/01

    DOI： 10.1093/nar/gku1163 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  38. COXPRESdb in 2015: coexpression database for animal species by DNA-microarray and RNAseq-based expression data with multiple quality assessment systems Peer-reviewed

    Yasunobu Okamura, Yuichi Aoki, Takeshi Obayashi, Shu Tadaka, Satoshi Ito, Takafumi Narise, Kengo Kinoshita

    Nucleic Acids Research　43　(D1)　D82　2014/11

    Publisher: Oxford University Press ({OUP})

    DOI： 10.1093/nar/gku1163 　

    ISSN： 1362-4962

  39. ATTED-II in 2014: Evaluation of Gene Coexpression in Agriculturally Important Plants Peer-reviewed

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Yuichi Aoki, Matsuyuki Shirota, Kengo Kinoshita

    Plant and Cell Physiology　55　(1)　e6　2014/01

    Publisher: Oxford University Press ({OUP})

    DOI： 10.1093/pcp/pct178 　

    ISSN： 1471-9053

  40. ATTED-II in 2014: Evaluation of Gene Coexpression in Agriculturally Important Plants Peer-reviewed

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Yuichi Aoki, Matsuyuki Shirota, Kengo Kinoshita

    PLANT AND CELL PHYSIOLOGY　55　(1)　e6　2014/01

    DOI： 10.1093/pcp/pct178 　

    ISSN： 0032-0781

    eISSN： 1471-9053

  41. BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains. Peer-reviewed

    Katayama T, Wilkinson MD, Aoki-Kinoshita KF, Kawashima S, Yamamoto Y, Yamaguchi A, Okamoto S, Kawano S, Kim JD, Wang Y, Wu H, Kano Y, Ono H, Bono H, Kocbek S, Aerts J, Akune Y, Antezana E, Arakawa K, Takagi T

    Journal of biomedical semantics　5　(1)　5　2014

    DOI： 10.1186/2041-1480-5-5 　

  42. COXPRESdb: a database of comparative gene coexpression networks of eleven species for mammals Peer-reviewed

    Takeshi Obayashi, Yasunobu Okamura, Satoshi Ito, Shu Tadaka, Ikuko N. Motoike, Kengo Kinoshita

    NUCLEIC ACIDS RESEARCH　41　(D1)　D1014-D1020　2013/01

    DOI： 10.1093/nar/gks1014 　

    ISSN： 0305-1048

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Misc. 12

  1. Abstract A041: Genetic landscape of intracholecystic papillary neoplasms (ICPNs) of the gallbladder-STK11 as a characteristic driver gene for ICPNs-

    Satomi Saito, Keigo Murakami, Taito Itoh, Yusuke Mizukami, Yusuke Ono, Yasunobu Okamura, Kengo Kinoshita, Michiaki Unno, Goro Honda, Toru Furukawa

    CANCER RESEARCH　86　(5)　2026/03/05

    DOI： 10.1158/1538-7445.RASONCOTHER26-A041 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  2. TRACING THE MOLECULAR EVOLUTION OF EARLY PANCREATIC CANCER WITH A COMPREHENSIVE MULTI-OMICS APPROACH

    Taito Itoh, Yuko Omori, Yusuke Ono, Okamura Yasunobu, Kenji Takahashi, Takashi Kokumai, Goro Honda, Hanada Keiji, Yasuhiro Shimizu, Namamura Masafumi, Kei Itoh, Mareyuki Endo, Yu Kasayose, Kengo Kinoshita, Atsushi Masamune, Michiaki Unno, Yusuke Mizukami, Toru Furukawa

    GASTROENTEROLOGY　169　(1)　2025/05/03

    ISSN： 0016-5085

    eISSN： 1528-0012

  3. 高異型度PanIN/膵上皮内癌・小径膵癌の分子進化モデル(Molecular evolutionary model of early pancreatic cancer)

    伊藤 泰斗, 大森 優子, 小野 裕介, 高橋 賢治, 岡村 容伸, 木下 賢吾, 正宗 淳, 海野 倫明, 水上 裕輔, 古川 徹

    日本病理学会会誌　113　(1)　318-318　2024/02

    Publisher: (一社)日本病理学会

    ISSN： 0300-9181

  4. 高異型度PanIN/膵上皮内癌・小径膵癌の分子進化モデル(Molecular evolutionary model of early pancreatic cancer)

    伊藤 泰斗, 大森 優子, 小野 裕介, 高橋 賢治, 岡村 容伸, 木下 賢吾, 正宗 淳, 海野 倫明, 水上 裕輔, 古川 徹

    日本病理学会会誌　113　(1)　318-318　2024/02

    Publisher: (一社)日本病理学会

    ISSN： 0300-9181

  5. Data-sharing by Data-visiting model. A proposal to realize data sharing of divergent, big and sensitive data

    木下賢吾, 木下賢吾, 木下賢吾, 岡村容伸, 岡村容伸

    実験医学　40　(6)　2022

    ISSN： 0288-5514

  6. 患者由来IPMNオルガノイドとゲノム解析を用いた増殖形態の解明

    椎原正尋, 石川智彦, 大森優子, 元井冬彦, 森川孝則, 中川圭, 林洋毅, 水間正道, 大塚英郎, 岡村容伸, 木下賢吾, 海野倫明, 古川徹

    日本外科学会定期学術集会(Web)　122nd　2022

  7. 長鎖リードシークエンス技術を用いた日本人構造多型パネルJSV1の構築

    大槻晃史, 大槻晃史, 岡村容伸, 岡村容伸, 勝岡史城, 勝岡史城, 木下賢吾, 木下賢吾, 木下賢吾, 木下賢吾, 山本雅之, 山本雅之, 山本雅之

    日本生化学会大会(Web)　95th　2022

  8. 膵胆道癌オルガノイドの個別化医療モデルへの活用

    椎原正尋, 椎原正尋, 樋口亮太, 岡村容伸, 木下賢吾, 山本雅一, 元井冬彦, 海野倫明, 古川徹

    日本癌学会学術総会抄録集(Web)　80th　2021

  9. Clinical Sequencing for Patients with Pancreatic Cancer

    Hideyuki Hayashi, Shigeki Tanishima, Ryo Mori, Yasunobu Okamura, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Dosaka-akita, Hiroshi Nishihara

    ANNALS OF ONCOLOGY　28　88-88　2017/10

    ISSN： 0923-7534

    eISSN： 1569-8041

  10. Clinical implementation of a comprehensive targeted amplicon sequencing system for cancer in Japan.

    Hideyuki Hayashi, Shigeki Tanishima, Ryo Mori, Yasunobu Okamura, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Akita, Hiroshi Nishihara

    JOURNAL OF CLINICAL ONCOLOGY　35　2017/05

    DOI： 10.1200/JCO.2017.35.15_suppl.e13115 　

    ISSN： 0732-183X

    eISSN： 1527-7755

  11. Gene module detection from the conservation of gene coexpression patterns among species

    2013　(5)　1-2　2013/03/14

  12. Comparative analysis of gene expression pattern between spieces

    Yasunobu Okamura, Takeshi Obayashi, Kengo Kinoshita

    IPSJ SIG technical reports　2012　(2)　1-2　2012/03/21

    Publisher: Information Processing Society of Japan (IPSJ)

    ISSN： 0919-6072

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    Currently gene expression data by DNA microarray are increasing. We can construct coexpression gene families from similarity of gene expression patterns. To find core functions for living organisms and divergent function of each spices, we compared similarity of gene expression patterns. Here we found that ribosomal protein or other house keeping genes are well conserved between human and mouse and that genes involved in nervous system and signal transductions are divergent.

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Research Projects 3

  1. Exploration of copy number variation associated with metabolic diseases challenged by the Japan Genome Cohort Alliance

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Nagoya University

    2025/04/01 - 2028/03/31

  2. ゲノム反復多型伸長変動と認知機能低下を伴う前臨床期神経変性筋疾患の遺伝病態の解明

    平良摩紀子, 岡村容伸, 布施昇男, 三木篤也, 田高周

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04 - 2027/03

  3. オルガノイド培養を応用した大腸癌に対する次世代個別化医療の実現に向けて

    唐澤 秀明, 大沼 忍, 山村 明寛, 黒羽 正剛, 小峰 啓吾, 岡村 容伸

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2024/03/31

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    本研究では、腫瘍とオルガノイドが同様の抗癌剤感受性を持つことが前提であり、まず腫瘍と対になるオルガノイドの遺伝子変異を次世代シークエンス（NGS）を用いて解析した。その結果、腫瘍で検出された遺伝子変異の98～99％がオルガノイドと重複しており、このことから、分子標的薬などの遺伝子変異に対する治療を評価する上で、オルガノイドは妥当な手段であると思われた。 続いて大腸癌組織におけるMAPK経路の遺伝子変異がMAPK経路の下流にあるERKを阻害するERK阻害薬（SCH772984）の感受性を規定するかどうかを検証した。大腸癌の発生・進行においてMAPK経路は重要な役割を果たしているが、BRAFやRASなどの遺伝子変異によって活性化されることが知られており、ERK阻害薬は、BRAFやKRAS変異のある癌細胞株に増殖抑制効果が示されている。 はじめに、14種類の大腸癌細胞株を用いて、SCH772984の薬剤感受性試験を行った。その結果、全てのBRAF変異細胞株で感受性を認めたが、KRAS変異細胞株は半数が耐性であった。 13症例の大腸癌切除検体より培養したオルガノイドに対してSCH772984の薬剤感受性試験を行ったところ、BRAFまたはKRAS変異症例の7例中6例がSCH772984に感受性を示し、BRAF・KRAS野生型の6例中5例は耐性であった。BRAF・KRAS遺伝子変異の有無により、オルガノイドのSCH772984感受性を予測できる傾向を認めたが、必ずしも一致しない症例も存在しており、遺伝子変異に基づくアプローチはあくまでも感受性予測に留まると考えられた。