Annual Report 2024
Division of Cancer Evolution
Kenichi Yoshida, June Takeda, Takuto Moori, Yusuke Tsumura, Yoshiaki Kurokawa, Kaito Mimura, Masataka Hasegawa, Chie Mori, Yumi Fujimoto, Akira Kaino, Kentaro Gosho, Marina Ohno, Yumiko Sema
Introduction
Almost all of cancers are caused by changes in the DNA sequence of the genomes. Recently, it has been reported that normal tissues acquire somatic mutations including driver mutations caused by aging and environmental exposures, leading to the clonal expansion of precancerous lesions. Therefore, it is critical to see the genetic alterations and clonal evolution not only in tumor tissues but also in normal tissues to understand the mechanisms of early carcinogenesis, achieve early detection of cancer and prevent cancer development.
The Team and What We Do
We are studying somatic mutations in normal tissues and cancers to understand the mechanisms of cancer development.
Research Activities
1. Genetic analysis of normal tissues
Whole-genome analysis of colonies derived from normal bronchial epithelial cells revealed the accumulation of mutations caused by endogenous DNA damage acquired in these bronchial epithelial cells (Spencer et al., Nature. 2025). Furthermore, we are generating organoids and colonies derived from single normal cells obtained from healthy individuals as well as from patients with hereditary cancer-predisposition syndromes, and performing genomic analyses of normal cells from tissues such as blood, bladder, and bronchial epithelium.
2. Cancer Genomics
Through genomic analysis of myeloid leukemia associated with Down syndrome (ML-DS), we identified novel driver alterations, including a partial tandem duplication in the RUNX1 gene, and demonstrated that genomic abnormalities in TP53 and CDKN2A are associated with poor prognosis (Sato, Yoshida et al., Blood. 2024). In addition, we are conducting comprehensive whole-genome sequencing studies of various cancers, including pediatric malignancies, such as hematological and renal tumors, as well as urological, lung, and breast cancers.
Education
We accepted one medical student and three postgraduate students for training and research.
Future Prospects
In the future, to understand the early carcinogenesis, we will study the somatic mutations in normal tissue of various organs from healthy donors and patients with familial cancers. For the study of cancer genomes, we will further analyze the whole-genome sequencing (WGS) data to detect non-coding driver variants as well as long-read sequencing data for identifying complex structural variants.
List of papers published in 2024
Journal
1. Sato T, Yoshida K, Toki T, Kanezaki R, Terui K, Saiki R, Ojima M, Ochi Y, Mizuno S, Yoshihara M, Uechi T, Kenmochi N, Tanaka S, Matsubayashi J, Kisai K, Kudo K, Yuzawa K, Takahashi Y, Tanaka T, Yamamoto Y, Kobayashi A, Kamio T, Sasaki S, Shiraishi Y, Chiba K, Tanaka H, Muramatsu H, Hama A, Hasegawa D, Sato A, Koh K, Karakawa S, Kobayashi M, Hara J, Taneyama Y, Imai C, Hasegawa D, Fujita N, Yoshitomi M, Iwamoto S, Yamato G, Saida S, Kiyokawa N, Deguchi T, Ito M, Matsuo H, Adachi S, Hayashi Y, Taga T, Saito AM, Horibe K, Watanabe K, Tomizawa D, Miyano S, Takahashi S, Ogawa S, Ito E. Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms. Blood, 143:2627-2643, 2024
2. Iyoda S, Yoshida K, Shoji K, Ito N, Tanaka M, Nannya Y, Yamato G, Tsujimoto S, Shiba N, Hayashi Y, Shiozawa Y, Shiraishi Y, Chiba K, Okada A, Tanaka H, Miyano S, Koga Y, Goto H, Moritake H, Terui K, Ito E, Kiyokawa N, Tomizawa D, Taga T, Tawa A, Takita J, Nishikori M, Adachi S, Ogawa S, Matsuo H. KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia. Leukemia, 38:1609-1612, 2024
3. Halik A, Tilgner M, Silva P, Estrada N, Altwasser R, Jahn E, Heuser M, Hou HA, Pratcorona M, Hills RK, Metzeler KH, Fenwarth L, Dolnik A, Terre C, Kopp K, Blau O, Szyska M, Christen F, Krönke J, Vasseur L, Löwenberg B, Esteve J, Valk PJM, Duchmann M, Chou WC, Linch DC, Döhner H, Gale RE, Döhner K, Bullinger L, Yoshida K, Damm F. Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients. Journal of hematology & oncology, 17:70, 2024