Annual Report 2023
Division of Genome Biology
Takashi Kohno, Kouya Shiraishi, Takashi Nakaoku, Kuniko Sunami, Masahiro Torasawa, Makoto Nishino, Junya Tabata, Tomoka Asami, Kosuke Maruyama, Shigenari Nukaga, Yu Hamaguchi, Ryoko Higashiyama, Akihumi Mochizuki, Rui Kitadai, Maiko Yamaguchi, Daiki Higuchi, Teruki Tsunashima, Atsushi Kawamura, Maiko Matsuda, Megumi Ishigami, Yuri Yamauchi, Yoko Shimada, Kazumi Uchiyama, Emi Ogawa, Nguyen Thai Le, Ayako Ui, Masayuki Shirasawa, Erika Machida, Erisa Fujii, Hourin Cho
Introduction
The goal of our research is to understand the genomic information of cancer cells and tissues as well as cancer patients and to understand their biological significance in order to elucidate the characteristics and properties of cancer and in order to identify and put into practice the seeds of cancer prevention, diagnosis, and treatment targets that will contribute to personalized medicine. The research is being conducted in collaboration with the staff of our center's hospitals and other institutions.
The Team and What We Do
The research is being conducted in collaboration with the staff of our center's hospitals and other institutions.
Research Activities
We conducted long-read genome sequencing analysis and single-cell spatial transcriptome analysis to elucidate the molecular mechanisms underlying malignant transformation of early lung tumors. To uncover the genetic factors promoting the development of EGFR mutation-positive lung cancer, which is prevalent among Asians, we performed a large-scale genome-wide association study. This study revealed that polymorphisms in the TERT gene and HLA class II genes are contributing factors (Figure 1). Additionally, we found that an HLA haplotype common in Asians is a risk factor for the development of several cancers, including HBV-positive liver cancer.
We conducted whole-genome sequencing projects on lung and breast cancers, identifying somatic genetic alterations that serve as therapeutic targets and candidate genes for genetic predisposition. As part of an international collaborative study on lung cancer, we identified genetic factors that determine the risk in non-smoking lung cancer patients, clarifying the differences from Western populations.
Through collaborative research with hospital staff, we elucidated molecular profiles associated with the efficacy of immune checkpoint inhibitors and clarified the relationship between the genomic profiles and clinical characteristics of various cancers.
Clinical Trials
We conducted a prospective whole-genome sequencing project in collaboration with the staff of National Cancer Center Hospital (UMIN000011141).
Education
We have mentored graduate students and young researchers with their research and presentation skills.
Future Prospects
Omics analysis of lung and other cancers is expected to identify target molecules that will contribute to the development of new prevention, diagnosis, and treatment modalities. We seek to contribute to promoting precision cancer medicine by linking this analysis with a gene panel test (NCC Oncopanel), which is conducted under Japan's national health insurance system.
List of papers published in 2023
Journal
1. 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. Nat Commun. 14(1):8375, 2023
2. Shi J, Shiraishi K (co-first author), Choi J, Matsuo K, Chen TY, Dai J, Hung RJ, Chen K, Shu XO, Kim YT, Landi MT, Lin D, Zheng W, Yin Z, Zhou B, Song B, Wang J, Seow WJ, Song L, Chang IS, Hu W, Chien LH, Cai Q, Hong YC, Kim HN, Wu YL, Wong MP, Richardson BD, Funderburk KM, Li S, Zhang T, Breeze C, Wang Z, Blechter B, Bassig BA, Kim JH, Albanes D, Wong JYY, Shin MH, Chung LP, Yang Y, An SJ, Zheng H, Yatabe Y, Zhang XC, Kim YC, Caporaso NE, Chang J, Ho JCM, Kubo M, Daigo Y, Song M, Momozawa Y, Kamatani Y, Kobayashi M, Okubo K, Honda T, Hosgood DH, Kunitoh H, Patel H, Watanabe SI, Miyagi Y, Nakayama H, Matsumoto S, Horinouchi H, Tsuboi M, Hamamoto R, Goto K, Ohe Y, Takahashi A, Goto A, Minamiya Y, Hara M, Nishida Y, Takeuchi K, Wakai K, Matsuda K, Murakami Y, Shimizu K, Suzuki H, Saito M, Ohtaki Y, Tanaka K, Wu T, Wei F, Dai H, Machiela MJ, Su J, Kim YH, Oh IJ, Lee VHF, Chang GC, Tsai YH, Chen KY, Huang MS, Su WC, Chen YM, Seow A, Park JY, Kweon SS, Chen KC, Gao YT, Qian B, Wu C, Lu D, Liu J, Schwartz AG, Houlston R, Spitz MR, Gorlov IP, Wu X, Yang P, Lam S, Tardon A, Chen C, Bojesen SE, Johansson M, Risch A, Bickeböller H, Ji BT, Wichmann HE, Christiani DC, Rennert G, Arnold S, Brennan P, McKay J, Field JK, Shete SS, Le Marchand L, Liu G, Andrew A, Kiemeney LA, Zienolddiny-Narui S, Grankvist K, Johansson M, Cox A, Taylor F, Yuan JM, Lazarus P, Schabath MB, Aldrich MC, Jeon HS, Jiang SS, Sung JS, Chen CH, Hsiao CF, Jung YJ, Guo H, Hu Z, Burdett L, Yeager M, Hutchinson A, Hicks B, Liu J, Zhu B, Berndt SI, Wu W, Wang J, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Wang WC, Xu J, Guan P, Tan W, Yu CJ, Yang G, Sihoe ADL, Chen Y, Choi YY, Kim JS, Yoon HI, Park IK, Xu P, He Q, Wang CL, Hung HH, Vermeulen RCH, Cheng I, Wu J, Lim WY, Tsai FY, Chan JKC, Li J, Chen H, Lin HC, Jin L, Liu J, Sawada N, Yamaji T, Wyatt K, Li SA, Ma H, Zhu M, Wang Z, Cheng S, Li X, Ren Y, Chao A, Iwasaki M, Zhu J, Jiang G, Fei K, Wu G, Chen CY, Chen CJ, Yang PC, Yu J, Stevens VL, Fraumeni JF Jr, Chatterjee N, Gorlova OY, Hsiung CA, Amos CI*, Shen H*, Chanock SJ*, Rothman N*, Kohno T*, Lan Q*. Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population. Nat Commun. 14(1):3043, 2023.
3. 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. Nat Commun. 14(1):4991, 2023
4. 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. Lancet Public Health. 8(9):e691-e700, 2023.
5. Asami Y, Kobayashi Kato M, Hiranuma K, Matsuda M, Shimada Y, Ishikawa M, Koyama T, Komatsu M, Hamamoto R, Nagashima M, Terao Y, Itakura A, Kohno T, Sekizawa A, Matsumoto K, Kato T, Shiraishi K, Yoshida H. Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer. Br J Cancer. 2023.
6. Ito T, Takayanagi D, Sekine S, Hashimoto T, Shimada Y, Matsuda M, Yamada M, Hamamoto R, Kato T, Shida D, Kanemitsu Y, Boku N, Kohno T, Takashima A, Shiraishi K. Comparison of clinicopathological and genomic profiles in anal squamous cell carcinoma between Japanese and Caucasian cohorts. Sci Rep. 2023, 13(1):3587.
7. Kanada R, Kagoshima Y, Suzuki T, Nakamura A, Funami H, Watanabe J, Asano M, Takahashi M, Ubukata O, Suzuki K, Aikawa T, Sato K, Goto M, Setsu G, Ito K, Kihara K, Kuroha M, Kohno T, Ogiwara H, Isoyama T, Tominaga Y, Higuchi S, Naito H. Discovery of DS-9300: A Highly Potent, Selective, and Once-Daily Oral EP300/CBP Histone Acetyltransferase Inhibitor. J Med Chem. 2023 Jan 12;66(1):695-715. doi: 10.1021/acs.jmedchem.2c01641.
8. Matsuzaki J, Kato K, Oono K, Tsuchiya N, Sudo K, Shimomura A, Tamura K, Shiino S, Kinoshita T, Daiko H, Wada T, Katai H, Ochiai H, Kanemitsu Y, Takamaru H, Abe S, Saito Y, Boku N, Kondo S, Ueno H, Okusaka T, Shimada K, Ohe Y, Asakura K, Yoshida Y, Watanabe SI, Asano N, Kawai A, Ohno M, Narita Y, Ishikawa M, Kato T, Fujimoto H, Niida S, Sakamoto H, Takizawa S, Akiba T, Okanohara D, Shiraishi K, Kohno T, Takeshita F, Nakagama H, Ota N, Ochiya T; Project Team for Development and Diagnostic Technology for Detection of miRNA in Body Fluids. Prediction of tissue-of-origin of early stage cancers using serum miRNomes. JNCI Cancer Spectr. 2023 Jan 3;7(1):pkac080.
9. Yotsukura M, Muraoka Y, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma. Ann Surg Oncol. 2023 Feb;30(2):851-858.
10. Yoshida T, Yatabe Y, Kato K, Ishii G, Hamada A, Mano H, Sunami K, Yamamoto N, Kohno T. The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan. Cancer Biol Med. 2023 May 3:j.issn.2095-3941.2023.0036.
11. Saito R, Kuroda T, Yoshida H, Sudo K, Saito M, Tanabe H, Takano H, Yamada K, Kiyokawa T, Yonemori K, Kato T, Okamoto A, Kohno T. Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma. Jpn J Clin Oncol. 53(9): 781-790, 2023.
12. Kawamura A, Matsuda K, Murakami Y, Saruta M, Kohno T, Shiraishi K. Contribution of an Asian-prevalent HLA haplotype to the risk of HBV-related hepatocellular carcinoma. Sci Rep. 13(1):12944, 2023.
13. Tabata M, Sato Y, Kogure Y, McClure MB, Oshikawa-Kumade Y, Saito Y, Shingaki S, Ito Y, Yuasa M, Koya J, Yoshida K, Kohno T, Miyama Y, Morikawa T, Chiba K, Okada A, Ogawa S, Ushiku T, Shiraishi Y, Kume H, Kataoka K. Inter- and intra-tumor heterogeneity of genetic and immune profiles in inherited renal cell carcinoma. Cell Rep. 42(7):112736, 2023.
14. Shirasawa M, Yoshida T, Shiraishi K, Goto N, Yagishita S, Imabayashi T, Matsumoto Y, Masuda K, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Yotsukura M, Yoshida Y, Nakagawa K, Naoki K, Tsuchida T, Hamamoto R, Yamamoto N, Motoi N, Kohno T, Watanabe SI, Ohe Y. Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer. Br J Cancer. 2023 Dec;129(12):2003-2013.
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 Med. 12(17):17835-17848, 2023.
16. Nakano S, Yamaji T, Shiraishi K, Hidaka A, Shimazu T, Kuchiba A, Saito M, Kunishima F, Nakaza R, Kohno T, Sawada N, Inoue M, Tsugane S, Iwasaki M. Smoking and risk of colorectal cancer according to KRAS and BRAF mutation status in a Japanese prospective Study. Carcinogenesis. 44(6):476-484, 2023.
17. Muraoka Y, Yotsukura M, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. Dynamics of recurrence after curative resection of nonsmall cell lung cancer. J Surg Oncol. 128(7):1205-1212, 2023. doi: 10.1002/jso.27395.
18. Higashiyama M, Motoi N, Yotsukura M, Yoshida Y, Nakagawa K, Yagishita S, Shirasawa M, Yoshida T, Shiraishi K, Kohno T, Ohe Y, Watanabe SI. Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma. Pathol Int. 73(5):188-197, 2023.
19. Kobayashi-Kato M, Fujii E, Asami Y, Ahiko Y, Hiranuma K, Terao Y, Matsumoto K, Ishikawa M, Kohno T, Kato T, Shiraishi K, Yoshida H. Utility of the revised FIGO2023 staging with molecular classification in endometrial cancer. Gynecol Oncol. 178:36-43, 2023.