Annual Report 2023
Department of Clinical Genomics
Kouya Shiraishi, Masahiro Gotoh, Hitoshi Ichikawa, Masaru Katoh, Kayoko Tao, Hanako Ono, Takashi Kubo, Mineko Ushiama, Sachiyo Mitani
Introduction
The aim of the Department of Clinical Genomics is to contribute to the improvement of genomic medicine for cancer patients through the development and implementation of next-generation sequencing (NGS)-based genomic tests and the identification of novel pathogenic variants and biomarkers from NGS analyses of cancer patient genomes. We provide genomic analysis services as a part of the core facility functions of the Fundamental Innovative Oncology Core (FIOC) of the National Cancer Center Research Institute (NCCRI). In collaboration with the Department of Biobank, we perform genome, transcriptome, and methylation analyses using clinical specimens as a one-stop service to support clinicians and basic researchers in their research.
The Team and What We Do
The purpose of the team is to provide genomic analysis support at the request of clinicians and researchers.
Research Activities
1. Research support for researchers and clinicians
The Department of Clinical Genomics provides technical support for genome analysis using clinical samples to clinicians and researchers affiliated with hospitals and research institutes inside and outside the center. In FY2023, we published 25 papers related to research support in peer-reviewed international journals. As part of our support for writing papers, we provided technical guidance on bioinformatics using R and Python and assisted with the creation of figures on behalf of clinicians and researchers.
2. Core facility genomic analysis services
We provide next-generation sequencing analysis services as part of the core facility function of the NCCR FIOC. In FY2023, we received 89 requests for genome analysis support from clinicians and researchers and performed whole-exome/whole-genome sequencing or transcriptome analysis of 4,609 samples. We also returned a wide range of analysis results, including somatic mutation detection, copy number analysis, and gene expression analysis, to clinicians and researchers.
Education
The Department of Clinical Genomics has accepted three graduate students as trainees.
Future Prospects
Having established a system to support genome analysis using clinical specimens, we plan to promote collaborative clinical research with companies in the future. We will continue to provide support for genome analysis in response to the needs of clinicians and researchers. Furthermore, we will focus on dry analysis and the training of personnel to perform it.
List of papers published in 2023
Journal
1. Shiraishi K, Takahashi A, Momozawa Y, Daigo Y, Kaneko S, Kawaguchi T, Kunitoh H, Matsumoto S, Horinouchi H, Goto A, Honda T, Shimizu K, Torasawa M, Takayanagi D, Saito M, Saito A, Ohe Y, Watanabe SI, Goto K, Tsuboi M, Tsuchihara K, Takata S, Aoi T, Takano A, Kobayashi M, Miyagi Y, Tanaka K, Suzuki H, Maeda D, Yamaura T, Matsuda M, Shimada Y, Mizuno T, Sakamoto H, Yoshida T, Goto Y, Yoshida T, Yamaji T, Sonobe M, Toyooka S, Yoneda K, Masago K, Tanaka F, Hara M, Fuse N, Nishizuka SS, Motoi N, Sawada N, Nishida Y, Kumada K, Takeuchi K, Tanno K, Yatabe Y, Sunami K, Hishida T, Miyazaki Y, Ito H, Amemiya M, Totsuka H, Nakayama H, Yokose T, Ishigaki K, Nagashima T, Ohtaki Y, Imai K, Takasawa K, Minamiya Y, Kobayashi K, Okubo K, Wakai K, Shimizu A, Yamamoto M, Iwasaki M, Matsuda K, Inazawa J, Shiraishi Y, Nishikawa H, Murakami Y, Kubo M, Matsuda F, Kamatani Y, Hamamoto R, Matsuo K, Kohno T. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses. Cancer communications (London, England), 44:287-293, 2024
2. Fukuda H, Arai K, Mizuno H, Nishito Y, Motoi N, Arai Y, Hiraoka N, Shibata T, Sonobe Y, Kayukawa Y, Hashimoto E, Takahashi M, Fujii E, Maruyama T, Kuwabara K, Nishizawa T, Mizoguchi Y, Yoshida Y, Watanabe SI, Yamashita M, Kitano S, Sakamoto H, Nagata Y, Mitsumori R, Ozaki K, Niida S, Kanai Y, Hirayama A, Soga T, Tsukada K, Yabuki N, Shimada M, Kitazawa T, Natori O, Sawada N, Kato A, Yoshida T, Yasuda K, Ochiai A, Tsunoda H, Aoki K. Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments. Cancer science, 115:1763-1777, 2024
3. Kato MK, Fujii E, Asami Y, Momozawa Y, Hiranuma K, Komatsu M, Hamamoto R, Ebata T, Matsumoto K, Ishikawa M, Kohno T, Kato T, Yoshida H, Shiraishi K. Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer. Cancer science, 115:1646-1655, 2024
4. Kojima N, Kubo T, Mori T, Satomi K, Matsushita Y, Iwata S, Yatabe Y, Ichimura K, Kawai A, Ichikawa H, Yoshida A. Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study. Virchows Archiv, 484:71-81, 2024
5. Odate T, Satomi K, Kubo T, Matsushita Y, Ueno T, Kurose A, Shomori K, Nakai T, Watanabe R, Segawa K, Ohshika S, Miyake N, Kudo S, Shimoi T, Kobayashi E, Komiyama M, Yoshimoto S, Nakatani F, Kawai A, Yatabe Y, Kohsaka S, Ichimura K, Ichikawa H, Yoshida A. Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases. Modern pathology, 37:100359, 2024
6. Makiuchi S, Tian Y, Fujimoto M, Kuramoto J, Tsuda N, Ojima H, Gotoh M, Hiraoka N, Yoshida T, Kanai Y, Arai E. DNA methylation alterations of ADCY5, MICAL2, and PLEKHG2 during the developmental stage of cryptogenic hepatocellular carcinoma. Hepatology research, 54:284-299, 2024
7. Nakamura W, Hirata M, Oda S, Chiba K, Okada A, Mateos RN, Sugawa M, Iida N, Ushiama M, Tanabe N, Sakamoto H, Sekine S, Hirasawa A, Kawai Y, Tokunaga K, Tsujimoto SI, Shiba N, Ito S, Yoshida T, Shiraishi Y. Assessing the efficacy of target adaptive sampling long-read sequencing through hereditary cancer patient genomes. NPJ genomic medicine, 9:11, 2024
8. Nishida T, Naito Y, Takahashi T, Saito T, Hisamori S, Manaka D, Ogawa K, Hirota S, Ichikawa H. Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors. Cancer science, 115:894-904, 2024
9. Blechter B, Wong JYY, Chien LH, Shiraishi K, Shu XO, Cai Q, Zheng W, Ji BT, Hu W, Rahman ML, Jiang HF, Tsai FY, Huang WY, Gao YT, Han X, Steinwandel MD, Yang G, Daida YG, Liang SY, Gomez SL, DeRouen MC, Diver WR, Reddy AG, Patel AV, Le Marchand L, Haiman C, Kohno T, Cheng I, Chang IS, Hsiung CA, Rothman N, Lan Q. Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity. British journal of cancer, 130:1286-1294, 2024
10. Aoki K, Nishito Y, Motoi N, Arai Y, Hiraoka N, Shibata T, Sonobe Y, Kayukawa Y, Hashimoto E, Takahashi M, Fujii E, Nishizawa T, Fukuda H, Ohashi K, Arai K, Mizoguchi Y, Yoshida Y, Watanabe SI, Yamashita M, Kitano S, Sakamoto H, Nagata Y, Mitsumori R, Ozaki K, Niida S, Kanai Y, Hirayama A, Soga T, Maruyama T, Tsukada K, Yabuki N, Shimada M, Kitazawa T, Natori O, Sawada N, Kato A, Yoshida T, Yasuda K, Mizuno H, Tsunoda H, Ochiai A. Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations. Cancer research communications, 3:1026-1040, 2023
11. Igarashi T, Mazevet M, Yasuhara T, Yano K, Mochizuki A, Nishino M, Yoshida T, Yoshida Y, Takamatsu N, Yoshimi A, Shiraishi K, Horinouchi H, Kohno T, Hamamoto R, Adachi J, Zou L, Shiotani B. An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress. Nature communications, 14:4991, 2023
12. Haga Y, Sakamoto Y, Kajiya K, Kawai H, Oka M, Motoi N, Shirasawa M, Yotsukura M, Watanabe SI, Arai M, Zenkoh J, Shiraishi K, Seki M, Kanai A, Shiraishi Y, Yatabe Y, Matsubara D, Suzuki Y, Noguchi M, Kohno T, Suzuki A. Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma. Nature communications, 14:8375, 2023
13. Hashimoto T, Takayanagi D, Yonemaru J, Naka T, Nagashima K, Machida E, Kohno T, Yatabe Y, Kanemitsu Y, Hamamoto R, Takashima A, Shiraishi K, Sekine S. A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer. British journal of cancer, 129:1176-1183, 2023
14. Imai T, Yoshida H, Machida Y, Kuramochi M, Ichikawa H, Kubo T, Takahashi M, Kato T. Alteration in molecular properties during establishment and passaging of endometrial carcinoma patient-derived xenografts. Scientific reports, 13:8511, 2023
15. Hiranuma K, Asami Y, Kato MK, Murakami N, Shimada Y, Matsuda M, Yazaki S, Fujii E, Sudo K, Kuno I, Komatsu M, Hamamoto R, Makinoshima H, Matsumoto K, Ishikawa M, Kohno T, Terao Y, Itakura A, Yoshida H, Shiraishi K, Kato T. Rare FGFR fusion genes in cervical cancer and transcriptome-based subgrouping of patients with a poor prognosis. Cancer medicine, 12:17835-17848, 2023
16. Kojima Y, Yoshida H, Okuya T, Okuma HS, Nishikawa T, Tanioka M, Sudo K, Noguchi E, Shimoi T, Tamura K, Tanase Y, Uno M, Ishikawa M, Arakaki M, Ichikawa H, Yagishita S, Hamada A, Fujiwara Y, Yonemori K, Kato T. Therapeutic target biomarkers of patient-derived xenograft models of gastric-type cervical adenocarcinoma. Gynecologic oncology reports, 50:101302, 2023
17. Kojima N, Mori T, Motoi T, Kobayashi E, Yoshida M, Yatabe Y, Ichikawa H, Kawai A, Yonemori K, Antonescu CR, Yoshida A. Frequent CD30 Expression in an Emerging Group of Mesenchymal Tumors With NTRK, BRAF, RAF1, or RET Fusions. Modern pathology, 36:100083, 2023
18. Sekita T, Yoshida A, Kawai A, Ichikawa H, Kobayashi E. IDH-negative chondrosarcoma with metachronous dedifferentiation only in the metastatic site-A diagnostic pitfall. Genes, chromosomes & cancer, 62:755-760, 2023
19. Tao K, Yamazaki F, Kubo T, Sunami K, Kumamoto T, Arakawa A, Sugiyama M, Watanabe Y, Nakajima M, Shirakawa N, Tanimura K, Koyama T, Hirata M, Sudo K, Tanabe N, Watanabe T, Yoshida T, Kitami M, Yoshida A, Yatabe Y, Nakano Y, Ohira M, Kamijo T, Nakazawa A, Kato M, Ichimura K, Kohno T, Yamamoto N, Hishiki T, Ichikawa H, Ogawa C. Pediatric Precision Medicine at the National Cancer Center Japan: Prospective Genomic Study of Pediatric Patients with Cancer as Part of the TOP-GEAR Project. JCO precision oncology, 7:e2200266, 2023
20. Miyazaki B, Ueno T, Sugiyama M, Kojima S, Arakawa A, Tao K, Tanimura K, Shiraishi K, Yagishita S, Kohsaka S, Kato M, Kiyokawa N, Goto Y, Yatabe Y, Hamada A, Mano H, Ogawa C, Tanaka Y. Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia. NPJ precision oncology, 7:132, 2023
21. Koyama T, Shimizu T, Kojima Y, Sudo K, Okuma HS, Shimoi T, Ichikawa H, Kohsaka S, Sadachi R, Hirakawa A, Yoshida A, Ando RM, Ueno T, Yanagaki M, Matsui N, Nakamura K, Yamamoto N, Yonemori K. Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study. Cancer discovery, 13:1814-1825, 2023
22. Oda S, Ushiama M, Nakamura W, Gotoh M, Tanabe N, Watanabe T, Odaka Y, Aoyagi K, Sakamoto H, Nakajima T, Sugano K, Yoshida T, Shiraishi Y, Hirata M. A complex rearrangement between APC and TP63 associated with familial adenomatous polyposis identified by multimodal genomic analysis: a case report. Frontiers in oncology, 13:1205847, 2023
23. Nikaido M, Takimoto T, Sakurai T, Hoki M, Minamiguchi S, Nakajima T, Torishima M, Nishigori T, Obama K, Koyama Y, Chiba T, Ushiama M, Gotoh M, Teramura M, Takeda H, Shimizu T, Seno H. Gastric juvenile polyposis syndrome with inflammatory changes in the intervening mucosa. Pathology international, 73:566-569, 2023
24. Kawamura M, Shirota H, Niihori T, Komine K, Takahashi M, Takahashi S, Miyauchi E, Niizuma H, Kikuchi A, Tada H, Shimada M, Kawamorita N, Kanamori M, Sugiyama I, Tsubata M, Ichikawa H, Yasuda J, Furukawa T, Aoki Y, Ishioka C. Management of patients with presumed germline pathogenic variant from tumor-only genomic sequencing: A retrospective analysis at a single facility. Journal of human genetics, 68:399-408, 2023
25. Fares AF, Li Y, Jiang M, Brown MC, Lam ACL, Aggarwal R, Schmid S, Leighl NB, Shepherd FA, Wang Z, Diao N, Wenzlaff AS, Xie J, Kohno T, Caporaso NE, Harris C, Ma H, Barnett MJ, Leal LF, Fernandez-Tardon G, Pérez-Ríos M, Davies MPA, Taylor F, Schöttker B, Brennan P, Zaridze D, Holcatova I, Lissowska J, Świątkowska B, Mates D, Savic M, Brenner H, Andrew A, Cox A, Field JK, Ruano-Ravina A, Shete SS, Tardon A, Wang Y, Le Marchand L, Reis RM, Schabath MB, Chen C, Shen H, Ryan BM, Landi MT, Shiraishi K, Zhang J, Schwartz AG, Tsao MS, Christiani DC, Yang P, Hung RJ, Xu W, Liu G. Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies. The Lancet. Public health, 8:e691-e700, 2023