Cancer is essentially a “disease of the genome” that develops and evolves 53Cycle of template insertionTERTTERTgeneLiver cancerTERT promoter or upstream regionwith 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 discovery of genom-ic biomarkers and personalized cancer medicine.Figure: Diverse structural variants (SVs) of the TERT gene that were found in a pan-cancer whole genome sequencing (PCAWG) projectCycles of “template insertion” of the TERT gene were identified in liver cancers (upper). Diverse SVs in the promoter or upstream region of the TERT gene were frequently observed in kidney cancers, hepatobiliary cancers, melanomas, and sarcomas (lower). SV break-point locations within the region ~100kb upstream of TERT. The curved line connects two breakpoints common to the same SV.Recent Major PublicationsKawasaki K, Toshimitsu K, Matano M, Fujita M, Fujii M, Togasaki K, Ebisudani T, Shimokawa M, Takano A, Takahasi S, Ohta Y, Nanki K, Igarashi R, Ishimaru K, Shida H, Sukawa Y, Saito Y, Sasagawa S, Lee H, Ha K, Fukunaga K, Tanabe M, Ishihara S, Hamamoto Y, Yasuda H, Sekine S, Kudo A, Kitagawa Y, Kanai T, Nakagawa H, and Sato T. An organoid biobank of rare human neuroendocrine neoplasms enables genotype-phenotype mapping. Cell 183, 1420-35 (2020)Fujimoto A*, Fujita M, Maejima K, Hasegawa T, Nakano K, Oku-Sasaki A, Wong J, Shiraishi Y, Miyano S, Imoto S, Akagi T, and Nakagawa H*. Comprehensive analysis of indels in whole-genome microsatellite regions and mi-crosatellite instability across 21 cancer types. Genome Res 30, 334-346 (2020)The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature 578, 82-93 (2020)Invited presentationsNakagawa H. “GWAS and polygenic risk score (PRS) for prostate cancer” The 64th Annual meeting of the Japan Society of Human Genomic (Nagoya, Japan) November 2020Nakagawa H. “Whole genome and immuno-genomic analysis of liver cancer” The 79th Annual meeting of the Japanese Cancer Association (Hiroshima, Japan) October 2020Nakagawa H. “Cancer Whole Genome Sequencing for Genomic Medicine” Annual meeting of Japan Society of Urologic Oncology (Kyoto, Japan) October 2020Nakagawa H. “Cancer Whole-Genome Sequencing” Annual meeting of The Japanese Society for Hereditary Cancer (Osaka, Japan) August 2020Laboratory for Cancer GenomicsTeam Leader: Hidewaki Nakagawa
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