1: Whole-genome landscape of adult T-cell leukemia/lymphoma.
Science of the Month - May 2022
Blood,
2022 Feb 17;139(7):967-982. doi: 10.1182/blood.2021013568.
Kogure Y, Kameda T, Koya J, Yoshimitsu M, Nosaka K, Yasunaga JI, Imaizumi Y, Watanabe M, Saito Y, Ito Y, McClure MB, Tabata M, Shingaki S, Yoshifuji K, Chiba K, Okada A, Kakiuchi N, Nannya Y, Kamiunten A, Tahira Y, Akizuki K, Sekine M, Shide K, Hidaka T, Kubuki Y, Kitanaka A, Hidaka M, Nakano N, Utsunomiya A, Sica RA, Acuna-Villaorduna A, Janakiram M, Shah U, Ramos JC, Shibata T, Takeuchi K, Takaori-Kondo A, Miyazaki Y, Matsuoka M, Ishitsuka K, Shiraishi Y, Miyano S, Ogawa S, Ye BH, Shimoda K, Kataoka K.
In recent years, international genomic analyses of cancer patient populations have been conducted, and the overall picture of driver abnormalities that form the basis of cancer development and progression is being elucidated. However, rare cancers such as adult T-cell leukemia/lymphoma (ATL), which is common in Japan, have not been sufficiently studied. We collected a total of 150 ATL samples from Japan and abroad and performed high-depth whole-genome analysis with enhanced detection power. By integratively analyzing multiple types of abnormalities, including mutations, structural abnormalities, and copy number abnormalities in protein-coding and non-coding regions, we identified 56 driver genes, including 11 novel genes such as the *CIC* and *REL* genes. Furthermore, using a mouse model, we showed that abnormalities specific to CIC-L (the long isoform) increase Foxp3-positive T cells, which are considered the origin of ATL development. This study, which also analyzed genomic abnormalities in ATL from various other perspectives, is expected to provide a basis for the development of new diagnostic methods and therapeutic drugs for ATL.
(Keisuke Kataoka, Department of Hematology, Department of Internal Medicine, Class of 1984)
2: Organoid screening reveals epigenetic vulnerabilities in human colorectal cancer.
Nature Chemical Biology.
Toshimitsu K, Takano A, Fujii M, Togasaki K, Matano M, Takahashi S, Kanai T, Sato T.
With improvements in sequencing technology, precision medicine, which advances treatment based on gene variants, has become a reality. How will medicine evolve in the future? In this study, we examined the in vitro drug sensitivity of 20 organoid lines established from colorectal cancer patients. As per current clinical evidence, colorectal cancer organoids with *KRAS* mutations showed resistance to EGFR antibody drugs. However, some colorectal cancer organoids did not follow the predictions of genomic medicine, suggesting the need to incorporate other parameters such as epigenomic changes. In fact, we found that sensitivity to paclitaxel, an anticancer drug, is determined by the epigenetic silencing of specific genes. Furthermore, this study achieved dramatic improvements in the amplification efficiency of patient-derived organoids, the throughput of drug sensitivity analysis, and the reduction of analysis time. These research findings are expected to lead to the emergence of organoid medicine, where tumors collected from patients are cultured directly to accurately predict drug sensitivity.
(Toshiro Sato, The Sakaguchi Laboratory, Department of Organoid Medicine, Class of 1976)
3: Research impact analysis of international funding agencies in the realm of allergy and immunology.
Allergy.
Takeya Adachi, Yasushi Ogawa, Tamami Fukushi, Kei Ito, Amane Koizumi, Masashi Shirabe, Masako Toriya, Jun Hirako, Takenori Inomata, Katsunori Masaki, Ryohei Sasano, Sakura Sato, Keigo Kainuma, Masaki Futamura, Keiko Kan-o, Yosuke Kurashima, Saeko Nakajima, Masafumi Sakashita, Hideaki Morita, Aikichi Iwamoto, Sankei Nishima, Mayumi Tamari, Hajime Iizuka
This study conducted a research impact analysis of the immunology and allergy programs of AMED, NIH, and MRC. It revealed that while research papers from Japan have volume and "research depth"—long-term influence—their open access rate is low. Previously, journal evaluation indices such as the impact factor have been misused in research grant evaluations. However, the analysis platform established based on the results of this study, which incorporates diverse perspectives, is expected to contribute to the formulation of effective international collaborative research and long-term research strategies.
(Takeya Adachi, Department of Dermatology, Class of 1986)