Cancer is essentially a “disease of the genome” that develops and evolves 56(8year)with the accumulation of a variety of mutations in its genetically unstable background. Some somatic mutations of driver genes have been successfully targeted for cancer treatment, and germline variants are related to cancer pre-disposition and risk assessment. Now, genotype-based personalized cancer therapy is in the clinical stage. Understanding of, and attention to, the underly-ing genetic diversity in cancer is, therefore, likely to increase the success of new cancer treatment modalities. Recent explosive advances in next-generation se-quencing (NGS) and bioinformatics enable us to perform systematic, genome-wide identification of all somatic abnormalities by whole genome sequencing (WGS) and RNA sequencing. Furthermore, cancer also has been proven to have features of an immune reaction and, thus, immune therapies targeting im-mune checkpoints and neo-antigens derived from somatically mutated proteins are also treatment realities. To explore whole genomic and immuno-genomic alterations and their diversity in cancer, we have been applying NGS and new single-cell technologies and analyzing these data through international collabo-rations such as the International Cancer Genome Consortium (ICGC). These approaches, combined with mathematical analysis and other -omics analyses, can clarify the underlying cancer genesis and cancer immunity and achieve a molecular sub-classification of cancer, which will facilitate the discovery of ge-nomic biomarkers and personalized cancer medicine.Figure: Landscape of driver mutations in childhood liver neo-plasms.134 cases of childhood hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are sorted by the age at diagnosis. The bar graph in the top panel shows individual age at diagnosis (childhood HCC, tween HB, child HB, infant HB). The middle panel details driver mutations in this cohort. (*) Mutations and in-frame deletions of CTNNB1 are frequently observed in HBs and TERT promoter mutations are prevalent in the tween HBs and HCCs.Recent Major PublicationsNagae G, Yamamoto Y, Fujita M, Fujita T, Umeda T, Fukuda S, Tatsuno K, Maejima K, Kurihara S, Kojima M, Hishiki T, Watanabe K, Ida K, Yano M, Hiyama Y, Tanaka Y, Inoue T, Ueda H, Nakagawa H*, Aburatani H*, and Hiyama E*. Genetic and epigenetic basis of hepatoblas-toma diversity. Nat Commun 12, 5423 (2021)Mizuno S, Yamaguchi R, Hasegawa T, Hayashi S, Fujita M, Zhang F, Koh Y, Lee SY, Yoon SS, Shimizu E, Komura M, Fujimoto A, Nagai M, Kato M, Liang H, Miyano S, Zhang Z, Nakagawa H*, and Imoto S*. Immuno-genomic pan-cancer landscape reveals immune escape mechanisms and immuno-editing histories. Sci Rep 11, 15713 (2021)Ebata N, Fujita M, Sasagawa S, Maejima K, Okawa Y, Hatanaka Y, Mitsuhashi T, Oosawa A, Tanaka H, Miyano S, Nakamura T, Hirano S*, and Nakagawa H*. Genomic and transcriptomic landscape of gallbladder cancer for molecular classification and tumor microenvironment characterization. Cancers (Basel) 13, 733 (2021)Invited presentationsNakagawa H. “Genomic Structures and Carcinogenesis of HBV Integrations in Liver Cancer” The Asian Pacific Association for the Study of the Liver (Tokyo, Japan) December 2021Nakagawa H. “Data Sharing in the International Genome Consortium” Illumina Genomics Summit 2021 (Tokyo, Japan/Online) November 2021Nakagawa H. “Whole genomics and Precision Oncology for Hepato-biliary Cancer” The Asian Pacific Association for the Study of the Liver (Osaka, Japan) September 2021Nakagawa H. “Immuno-genomic Analysis of Cancer Tissues to Understand Tumor Immunology” The 25th Annual Meeting of the Japanese Association of Cancer Immunology (Wakayama, Japan) July 2021Nakagawa H. “Whole Genome Sequencing analysis and Clinical Implication for Liver Cancer” The 57th Annual Meeting of Liver Cancer Study Group of Japan (Kagoshi-ma, Japan) July 2021Laboratory for Cancer GenomicsTeam Leader: Hidewaki Nakagawa
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