Annual Report 2022
Division of Cancer Evolution
Kenichi Yoshida, Kentaro Gosho
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 the 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 have developed the methods of generating single cell-derived samples from normal tissues and those of collecting small samples using laser-capture microdissection to study somatic mutations in normal tissues. We further established the method to perform whole-genome sequencing using the DNA samples extracted from samples using the methods noted above.
2. Cancer Genomics
We conducted genetic analysis of acute erythroid leukemia (AEL) and identified complex rearrangements involving JAK2 and EPOR in the TP53-mutated subtype with the worst prognosis. We further demonstrated that these tumors can be target of JAK inhibitors using the patient-derived xenograft (PDX) models (Takeda, Yoshida et al., Blood Cancer Discov. 2022). We also studied the other types of cancers such as myxofibrosarcoma and characterized their genetic alterations (Takeuchi, Yoshida et al., Int J Cancer. 2022).
Future Prospects
In future, to understand the early carcinogenesis, we will study the somatic mutations in normal tissue of various organs using the systems which we have developed. For the study of cancer genomes, we will study the whole-genome sequencing (WGS) data of pediatric cancers and hematological malignancies as part of the national WGS project conducted by Japan Agency for Medical Research and Development (AMED). We will also study lesions which had been difficult to study, such as small precancerous lesions, using new techniques.
List of papers published in 2022
Journal
1. Isobe T, Takagi M, Sato-Otsubo A, Nishimura A, Nagae G, Yamagishi C, Tamura M, Tanaka Y, Asada S, Takeda R, Tsuchiya A, Wang X, Yoshida K, Nannya Y, Ueno H, Akazawa R, Kato I, Mikami T, Watanabe K, Sekiguchi M, Seki M, Kimura S, Hiwatari M, Kato M, Fukuda S, Tatsuno K, Tsutsumi S, Kanai A, Inaba T, Shiozawa Y, Shiraishi Y, Chiba K, Tanaka H, Kotecha RS, Cruickshank MN, Ishikawa F, Morio T, Eguchi M, Deguchi T, Kiyokawa N, Arakawa Y, Koh K, Aoki Y, Ishihara T, Tomizawa D, Miyamura T, Ishii E, Mizutani S, Wilson NK, Göttgens B, Miyano S, Kitamura T, Goyama S, Yokoyama A, Aburatani H, Ogawa S, Takita J. Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia. Nature communications, 13:4501, 2022
2. Takeuchi Y, Yoshida K, Halik A, Kunitz A, Suzuki H, Kakiuchi N, Shiozawa Y, Yokoyama A, Inoue Y, Hirano T, Yoshizato T, Aoki K, Fujii Y, Nannya Y, Makishima H, Pfitzner BM, Bullinger L, Hirata M, Jinnouchi K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Okamoto T, Haga H, Ogawa S, Damm F. The landscape of genetic aberrations in myxofibrosarcoma. International journal of cancer, 151:565-577, 2022
3. Yaguchi T, Kimura S, Sekiguchi M, Kubota Y, Seki M, Yoshida K, Shiraishi Y, Kataoka K, Fujii Y, Watanabe K, Hiwatari M, Miyano S, Ogawa S, Takita J. Description of longitudinal tumor evolution in a case of multiply relapsed clear cell sarcoma of the kidney. Cancer reports (Hoboken, N.J.), 5:e1458, 2022
4. Takeda J, Yoshida K, Nakagawa MM, Nannya Y, Yoda A, Saiki R, Ochi Y, Zhao L, Okuda R, Qi X, Mori T, Kon A, Chiba K, Tanaka H, Shiraishi Y, Kuo MC, Kerr CM, Nagata Y, Morishita D, Hiramoto N, Hangaishi A, Nakazawa H, Ishiyama K, Miyano S, Chiba S, Miyazaki Y, Kitano T, Usuki K, Sezaki N, Tsurumi H, Miyawaki S, Maciejewski JP, Ishikawa T, Ohyashiki K, Ganser A, Heuser M, Thol F, Shih LY, Takaori-Kondo A, Makishima H, Ogawa S. Amplified EPOR/JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia. Blood cancer discovery, 3:410-427, 2022
5. Yamato G, Kawai T, Shiba N, Ikeda J, Hara Y, Ohki K, Tsujimoto SI, Kaburagi T, Yoshida K, Shiraishi Y, Miyano S, Kiyokawa N, Tomizawa D, Shimada A, Sotomatsu M, Arakawa H, Adachi S, Taga T, Horibe K, Ogawa S, Hata K, Hayashi Y. Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia. Blood advances, 6:3207-3219, 2022
6. Kaburagi T, Yamato G, Shiba N, Yoshida K, Hara Y, Tabuchi K, Shiraishi Y, Ohki K, Sotomatsu M, Arakawa H, Matsuo H, Shimada A, Taki T, Kiyokawa N, Tomizawa D, Horibe K, Miyano S, Taga T, Adachi S, Ogawa S, Hayashi Y. Clinical significance of RAS pathway alterations in pediatric acute myeloid leukemia. Haematologica, 107:583-592, 2022