Cancer is essentially a “disease of the genome” that develops and evolves -0.8-0.40.40.8054Male Eos.Female Eos.Female othersMale othersPathway activitywith 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. Now, genotype-based personalized cancer ther-apy is in the clinical stage. Understanding of, and attention to, the underlying genetic diversity in cancer is, therefore, likely to increase the success of new cancer treatment modalities. Our whole genome sequencing (WGS), RNA se-quencing (RNA-seq) and bioinformatics enable us to characterize each type of cancer at the molecular level and to identify biomarkers and new therapeutic targets. We adopted a machine learning or AI algorithm to predict the clinical outcome of cancer by using cancer genome and transcriptome data. Further-more, cancer also has been proven to be an “immune disease”, with a variety of features of immune reactions, and immune therapies targeting immune check-points and neo-antigens derived from somatically mutated proteins are also treatment realities. To explore whole genomic and immuno-genomic alterations and their diversity in human cancer, we have been utilizing WGS and RNA-seq data from cancer tissues. These approaches, combined with recent single-cell RNAseq (scRNAseq) and spatial transcriptome (ST) analysis of cancer tissues, can clarify the underlying carcinogenesis and cancer immunology and achieve a molecular sub-classification of cancer, which will facilitate the discovery of biomarkers and personalized cancer medicine.Recently, somatic or mosaic mutations have also been recognized to occur in non-tumor tissues and involve disease status. By utilizing new analysis meth-ods that we developed for cancer genomics, we detected and analyzed somatic or mosaic mutations in several brain disease and vessel disease tissues, such as brain aneurysm (Science Trans Med 2023). We also performed ST and scRNA analysis on these mosaic-mutated tissues to understand their pathological and biological significance. Mosaic mutations in non-cancer disease tissues can il-luminate new human disease genomics.Figure: Immune cell scRNAseq profiles from a female esophageal squamous cell carcinoma (ESCC) tissue. (left) UMAPs rep-resent eosinophil-like clusters with the red dots indicating eosinophil-like cells from the female sample. (right) Hall-mark gene sets in female eosinophil-like cells compared with male eosinophil-like cells. Androgen, estrogen, and PI3K pathways (arrowheads) are gender-differentially activated in eosinophils but not in other immune cells.Recent Major PublicationsOkawa Y, Sasagawa S, Johnson TA, Kato H, Nagaoka K, Kobayashi Y, Hayashi A, Shibayama T, Maejima K, Tanaka H, Miyano S, Shibahara J, Nishizuka SS, Hirano S, Seto Y, Iwaya T, Kakimi K, Yasuda T, and Nakagawa H*. Immuno-genomic analysis reveals eosinophilic feature and favorable prognosis of female non-smoking esophageal squamous cell carcinomas. Cancer Letters 581, 216499 (2024)Jikuya R, Johnson TA, Maejima K, An J, Ju YS, Lee H, Kim Y, Okawa Y, Sasagawa S, Kanazashi Y, Fujita M, Imoto S, Mitome T, Ohtake S, Noguchi G, Kawaura S, Iribe Y, Aomori K, Tatenuma T, Komeya M, Ito H, Ito Y, Muraoka K, Furuya M, Kato I, Fujii S, Hamanoue H, Tamura T, Baba M, Suda T, Ko-dama T, Makiyama K, Yao M, Such BM, Ricketts CJ, Schmidt LS, Linehan WM, Nakagawa H*, Hasumi H*. Comparative analyses define differences between BHD-associated kidney cancer and sporadic chromophobe renal cell carcinoma. EBioMed 92, 104596 (2023)Shima Y, Sasagawa S, Ohta N, Oyama R, Sogawa C, Kim Y, Sakashita-Kubota M, Kawakami H, Naemura K, Takubo N, Kobayashi M, Ozeki A, Nakaki R, Tanaka M, Kamatani Y, Matsuda K, Kurihara H, Furihata T, Takahashi S, Rikitake Y, Kozaki K, Nakafuku M, Mataga N, Ohtsuka N, Akimitsu N, Wada Y, Kamiguchi H, Okabe S, Kato T, Nakagawa H, Saito N, Nakatomi H. Increased PDGFRB and NF-κB signaling caused by highly prevalent somatic mutations in intracranial aneu-rysms. Science Trans Med 15, eabq77218 (2023)Invited presentationsNakagawa H. “Spatial Transcriptomics, Genomics, and Biol-ogy of Non-tumor Disease Tissues” Spatial Biology Congress Asia (Singapore) November 2023Nakagawa H. “Whole Genome Sequencing Analysis and its Clinical Utility for GI Cancer” Special Lecture at Japan Digestive Disease Week (JDDW) Meeting (Kobe, Japan) November 2023Nakagawa H. “Somatic Mutational Signatures and Their Associations with Asian Cancer Etiology and Phenotypes” Human Genomics Asia / The 68th Annual meeting of The Japan Society of Human Genomics (Tokyo, Japan) October 2023Nakagawa H. “Whole Genome Portfolio of Biliary Tract Cancers” Special Lecture at the 59th Annual Meeting of the Japan Biliary Association (Sapporo, Japan) September 2023Nakagawa H. “Whole Genome Sequencing Analysis and its Clinical Utility for Liver Cancer” Special Lecture at the 58th Annual Meeting of Liver Cancer Study Group of Japan (Osaka, Japan) July 2023EosinophilLaboratory for Cancer GenomicsTeam Leader: Hidewaki Nakagawa
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