Annual Report 2023
Division of Cancer Evolution
Kenichi Yoshida, Mayu Morishita, Yoshiaki Kurokawa, Kaito Mimura, Kentaro Gosho, Ryo Okuse, Marin 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 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
We studied genetic alterations in normal breast epithelial cells and their clonal evolution using high-throughput sequencing technologies with small sampling technique and single-cell derived organoids, and found that founder clones of breast cancers with der(1;16) often develop from early puberty to late adolescence (Nishimura et al., Nature. 2023). We are further conducting genetic analysis of normal blood, bladder and bronchial cells using whole-genome sequencing of single cell-derived organoids/colonies.
2. Cancer Genomics
We conducted genetic analysis of primary mediastinal large B-cell lymphoma, which is one of the subtypes of malignant lymphoma, and revealed mutations in a novel driver gene ZNF217 and the associations between driver mutations and patients’ outcome (Briest et al., Leukemia. 2023; Noerenberg et al., J Clin Oncol. 2024). We are involved in the nationwide whole-genome sequencing study and conducting the genetic study of childhood cancers and upper urinary tract urothelial carcinomas.
Education
We accepted one medical student and three postgraduate students for training and research.
Future Prospects
In 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 to understand the mechanisms of early carcinogenesis. For the study of cancer genomes, we will further study the whole-genome sequencing (WGS) data of pediatric cancers and upper urinary tract urothelial carcinomas to unveil the functional role of the non-coding driver mutations. We will also study complex structural variants in detail using long-read sequencing technologies.
List of papers published in 2023
Journal
1. Noerenberg D, Briest F, Hennch C, Yoshida K, Hablesreiter R, Takeuchi Y, Ueno H, Staiger AM, Ziepert M, Asmar F, Locher BN, Toth E, Weber T, Amini RM, Klapper W, Bouzani M, Poeschel V, Rosenwald A, Held G, Campo E, Ishaque N, Stamatopoulos K, Kanellis G, Anagnostopoulos I, Bullinger L, Goldschmidt N, Zinzani PL, Bödör C, Rosenquist R, Vassilakopoulos TP, Ott G, Ogawa S, Damm F . Genetic Characterization of Primary Mediastinal B-Cell Lymphoma: Pathogenesis and Patient Outcomes . Journal of clinical oncology, 42:452-466 , 2024
2. Aoki T, Shiba N, Tsujimoto S, Yamato G, Hara Y, Kato S, Yoshida K, Ogawa S, Hayashi Y, Iwamoto S, Taki T, Shimada A, Iijima-Yamashita Y, Horibe K, Tawa A, Taga T, Adachi S, Tomizawa D . High IL2RA/CD25 expression is a prognostic stem cell biomarker for pediatric acute myeloid leukemia without a core-binding factor . Pediatric blood & cancer, 71:e30803 , 2024
3. Nannya Y, Tobiasson M, Sato S, Bernard E, Ohtake S, Takeda J, Creignou M, Zhao L, Kusakabe M, Shibata Y, Nakamura N, Watanabe M, Hiramoto N, Shiozawa Y, Shiraishi Y, Tanaka H, Yoshida K, Kakiuchi N, Makishima H, Nakagawa M, Usuki K, Watanabe M, Imada K, Handa H, Taguchi M, Kiguchi T, Ohyashiki K, Ishikawa T, Takaori-Kondo A, Tsurumi H, Kasahara S, Chiba S, Naoe T, Miyano S, Papaemanuil E, Miyazaki Y, Hellström-Lindberg E, Ogawa S. Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms. Blood advances, 7:3624-3636, 2023
4. Hara Y, Shiba N, Yoshida K, Yamato G, Kaburagi T, Shiraishi Y, Ohki K, Shiozawa Y, Kawamura M, Kawasaki H, Sotomatsu M, Takizawa T, Matsuo H, Shimada A, Kiyokawa N, Tomizawa D, Taga T, Ito E, Horibe K, Miyano S, Adachi S, Taki T, Ogawa S, Hayashi Y. TP53 and RB1 alterations characterize poor prognostic subgroups in pediatric acute myeloid leukemia. Genes, chromosomes & cancer, 62:412-422, 2023
5. Nishimura T, Kakiuchi N, Yoshida K, Sakurai T, Kataoka TR, Kondoh E, Chigusa Y, Kawai M, Sawada M, Inoue T, Takeuchi Y, Maeda H, Baba S, Shiozawa Y, Saiki R, Nakagawa MM, Nannya Y, Ochi Y, Hirano T, Nakagawa T, Inagaki-Kawata Y, Aoki K, Hirata M, Nanki K, Matano M, Saito M, Suzuki E, Takada M, Kawashima M, Kawaguchi K, Chiba K, Shiraishi Y, Takita J, Miyano S, Mandai M, Sato T, Takeuchi K, Haga H, Toi M, Ogawa S. Evolutionary histories of breast cancer and related clones. Nature, 620:607-614, 2023
6. Takagi M, Hoshino A, Bousset K, Röddecke J, Martin HL, Folcut I, Tomomasa D, Yang X, Kobayashi J, Sakata N, Yoshida K, Miyano S, Ogawa S, Kojima S, Morio T, Dörk T, Kanegane H . Bone Marrow Failure and Immunodeficiency Associated with Human RAD50 Variants . Journal of clinical immunology, 43:2136-2145 , 2023
7. Briest F, Noerenberg D, Hennch C, Yoshida K, Hablesreiter R, Nimo J, Sasca D, Kirchner M, Mansouri L, Inoue Y, Wiegand L, Staiger AM, Casadei B, Korkolopoulou P, Weiner J, Lopez-Guillermo A, Warth A, Schneider T, Nagy Á, Klapper W, Hummel M, Kanellis G, Anagnostopoulos I, Mertins P, Bullinger L, Rosenquist R, Vassilakopoulos TP, Ott G, Ogawa S, Damm F . Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma . Leukemia, 37:2237-2249 , 2023