Lab Activities

Laboratory for Genotyping Development

Research Activities

Yukihide Momozawa portrait

Team Director

Yukihide Momozawa

The Laboratory for Genotyping Development aims to generate and interpret large-scale genomic and functional validation evidence for personalized medicine. In 2025, we published 24 peer‑reviewed papers, including six in which laboratory members played leading roles.

We have contributed to personalized medicine for hereditary cancer by providing genetic evidence supporting clinical decision-making from more than 100,000 samples. In 2025, we published two key papers quantifying cancer-type risks and clinical and demographic features of pathogenic variant carriers across 23 cancers on a pan-cancer evaluation of CHEK2 (Takehara et al., 2025) and Lynch syndrome–associated mismatch-repair genes (Mizukami et al., 2025). These results are expected to be included in clinical guidelines to contribute to better personalized medicine as has been the case for our previous works.

We also addressed TP53-mutant clonal hematopoiesis (TP53-CHIP). TP53-CHIP was associated with poorer overall survival and elevated disease-specific mortality extending beyond myeloid neoplasms, including respiratory disease (Figure). Significant interactions accompanied by excess risks were observed between TP53-CHIP and lifestyle factors for disease-specific mortality. These findings elucidate aspects of disease pathogenesis and inform personalized risk management (Usui et al., 2025).

Finally, we extended our framework to veterinary medicine because a better understanding of genetic contribution to diseases and other phenotypes in dogs and cats could also benefit humans. We have identified several coding variants in canine pharmacogenes such as CYP2C21 and CYP2B6 and demonstrated that these variants altered enzymatic activity (Uno et al., 2025a,b). This highlights breed- and individual-level variability that can influence both veterinary anesthesia and the interpretation of dog-based drug metabolism.

TP53-CHIP risk of mortality overall and across major disease categories

Laboratory for Genotyping Development figure

TP53-CHIP risk of mortality overall and across major disease categories

Laboratory for Genotyping Development figure

****, q < 0.001 (Benjamini–Hochberg multiple test correction)

****, q < 0.001 (Benjamini–Hochberg multiple test correction)

Recent Major Publications

  1. Usui Y, Endo M, Iwasaki Y, Iijima H, Nakagawa H, Matsuda K, Momozawa Y. Clinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases. Blood Cancer Discov 6, 298–306 (2025)

  2. Mizukami K, Usui Y, Iwasaki Y, Shiraishi K, Hirata M, Kamatani Y, Endo M, Takahashi S, Mochizuki Y, Yamaguchi M, Kohno T, Matsuda K, Sugano K, Yoshida T, Nakagawa H, Terao C, Koyanagi YN, Matsuo K, Murakami Y, Spurdle AB, Momozawa Y. Pan-cancer prevalence, risk, and clinical and demographic characteristics of Lynch Syndrome-associated variants in BioBank Japan. Commun Med (Lond) 5, 522 (2025)

  3. Takehara Y, Usui Y, Stolařová L, Kleiblova P, Iwasaki Y, Johnson TA, Hirata M, Kamatani Y, Murakami Y, Endo M, Shiraishi K, Kohno T, Sugano K, Matsuda K, Yoshida T, Spurdle AB, Nakagawa H, Macurek L, Kleibl Z, Momozawa Y. Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2: Risk Estimation and Clinical Recommendations in East Asia. JCO Precis Oncol 9, e2400945 (2025)

  4. Sasagawa H, Narita S, Matsuda K, Kosaka T, Momozawa Y. Revisiting the impact of BRCA1 pathogenic variants on the aggressiveness of prostate cancer. JNCI Cancer Spectr 10, pkaf118 (2025)

  5. Uno Y, Fukunaga K, Mizukami K, Aoi T, Mushiroda T, Momozawa Y, Yamazaki H. Genetic variants in dog cytochrome P450 2B6 and their relevance to interindividual variability of oxidations of probe drug propofol. Drug Metab Dispos 53, 100189 (2025)

  6. Uno Y, Fukunaga K, Ushirozako G, Murayama N, Mizukami K, Aoi T, Tomiyasu H, Honnami M, Tsujimoto H, Sakaguchi M, Hisasue M, Mushiroda T, Momozawa Y, Yamazaki H. Genetic variants of cytochrome P450 2C21 identified by screening 6344 dogs influenced oxidations of the probe drug omeprazole. Biochem Pharmacol 242, 117394 (2025)

  7. Jikuya R, Johnson TA, Muraoka E, Noguchi G, Maekawa S, Obara W, Numakura K, Habuchi T, Maejima K, Sasagawa S, Kanazashi Y, Lee H, Song WJ, Sasagawa H, Mitome T, Ohtake S, Kawaura S, Iribe Y, Aomori K, Nagasaka H, Tatenuma T, Ueno D, Komeya M, Ito H, Ito Y, Muraoka K, Kawahara T, Furuya M, Kato I, Hamanoue H, Nishiyama A, Tamura T, Baba M, Suda T, Kodama T, Ogawa T, Uemura H, Yao M, Tsuzuki T, Nagashima Y, Miura Y, Kimura G, Imoto S, Momozawa Y, Fujii S, Makiyama K, Hasegawa T, Shuch BM, Ricketts CJ, Schmidt LS, Linehan WM, Nakagawa H, Hasumi H. Comparative transcriptome atlas as an assistive modality for complex classification of rare kidney cancers. Nat Commun 16, 10340 (2025)

  8. Enzan N, Miyazawa K, Koyama S, Kurosawa R, Ieki H, Yoshida H, Takechi F, Fukuyama M, Osako R, Tomizuka K, Liu X, Ozaki K, Onouchi Y; BioBank Japan Project; Matsuda K, Momozawa Y, Aburatani H, Kamatani Y, Yamaguchi T, Akazawa H, Node K, Ellinor PT, Levin MG, Damrauer SM, Voight BF, Joseph J, Sun YV, Terao C, Ninomiya T, Komuro I, Ito K. Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population. Nat Commun 16, 9680 (2025)

  9. Koyanagi Y, Murakami Y, Kominami T, Fukushima M, Goto K, Yokota S, Mizobuchi K, Mawatari G, Torii K, Inoue Y, Ota J, Okuda D, Fujiwara K, Yamaga H, Hisai T, Endo M, Iijima H, Kaida T, Miyata K, Nakazaki S, Hayashi T, Hirami Y, Akiyama M, Terao C, Momozawa Y, Sonoda K, Nishiguchi KM, Ikeda Y. Clinical characteristics of EYS-associated retinal dystrophy in 291 Japanese patients. NPJ Genom Med 11, 3 (2025)

  10. Yazaki S, Kitadai R, Momozawa Y, Yoshida T, Yamanaka T, Shiino S, Yamauchi C, Harano K, Saito M, Hirotsu Y, Aiba H, Hamamoto R, Shimizu C, Shimomura A, Shimoi T, Sudo K, Yoshida M, Sunami K, Shiraishi Y, Kuchiba A, Hori M, Katanoda K, Takata S, Ogawa A, Torasawa M, Mochizuki A, Shimada Y, Hiranuma K, Fujii E, Hirata M, Yamashita Y, Kogawa T, Murata T, Fujiwara S, Miyagi Y, Nakagomi H, Tachibana K, Matsuda K, Murakami Y, Tokunaga K, Kawai Y, Project BJ, Omata M, Ohtake T, Suto A, Onishi T, Naito Y, Yamashita T, Yonemori K, Kohno T, Shiraishi K. Germline variants of the POLH and RAD51 genes are candidate variants associated with risk of hormone receptor-negative young-onset breast cancer. NPJ Breast Cancer 11, 133 (2025)

  11. Blechter B, Wang X, Dai J, Karsonaki C, Shi J, Shiraishi K, Choi J, Matsuo K, Chen T, Hung RJ, Chen K, Shu X, Kim YT, Choudhury PP, Williams J, Landi MT, Lin D, Zheng W, Yin Z, Zhou B, Wang J, Seow WJ, Song L, Chang I, Hu W, Chien L, Cai Q, Hong Y, Kim HN, Wu Y, Wong MP, Richardson BD, Li S, Zhang T, Breeze C, Wang Z, Bassig BA, Kim JH, Albanes D, Wong Sm JY, Shin M, Chung LP, Yang Y, Zheng H, Dai H, Yatabe Y, Zhang X, Kim Y, Caporaso NE, Chang J, Ho JC, Daigo Y, Momozawa Y, Kamatani Y, Kobayashi M, Okubo K, Honda T, ..., Chatterjee N, Gorlova OY, Amos CI, Shen H, Hsiung CA, Chanock SJ, Rothman N, Kohno T, Lan Q, Zhang H. Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers. J Natl Cancer Inst djaf272 (2025)

  12. Yazaki S, Hori M, Aiba H, Momozawa Y, Yoshida M, Shiino S, Harano K, Yamauchi C, Yamanaka T, Miwa M, Matsuda K, Kawai Y, Kobayashi-Kato M, Kitagawa M, Saito M, Nakagomi H, Tachibana K, Sakamoto I, Takahashi K, Asami Y, Katanoda K, Kuchiba A, Yoshida H, Ishikawa M, Shimoi T, Sudo K, Shimizu C, ..., Suto A, Yonemori K, Kohno T, Shiraisihi K; BioBank Japan Project, Momozawa Y, Matsuda K, Iwasaki Y, Aoi T, Takata S, Murakami Y; NCBN Controls WGS Consortium, Kawai Y, Noiri E, Omae Y, Tokunaga K. Impact of germline variants on breast and ovarian cancer risk in Japanese women: an original cohort study and meta-analysis. EBioMedicine 116, 105758 (2025)

  13. Zhao Y, Hisayoshi T, Zhang D, Suzuki S, Watanabe T, Kobayashi A, Guo Q, Momozawa Y, Shimokawa T, Kato S, Miki Y, Sunada S. Steroid-Modulated Transcription Synergistically Forms DNA Double-Strand Breaks With Topoisomerase II Inhibitor. Cancer Sci 116, 1952-1962 (2025)

  14. Cho H, Shiraishi K, Sunami K, Momozawa Y, Yoshida T, Matsumoto S, Matsuda K, Saito M, Goto A, Honda T, Mochizuki A, Torasawa M, Daigo Y, Shimizu K, Kunitoh H, Yoshida Y, Hirata M, Shimada Y, Ueki M, Ono H, Gotoh M, Igawa YS, Tateishi A, Yamaguchi Y, Higashiyama RI, Machida E, Iwasaki M, Kawai Y, Yasuda H, Hamamoto J, ..., Goto Y, Horinouchi H, Miyazaki Y, Ito H, Nagashima T, Ohtaki Y, Imai K, Minamiya Y, Okubo K, Inazawa J, Shiraishi Y, Tokunaga K, Kamatani Y, Yatabe Y, Goto K, Tsuboi M, Watanabe S, Ohe Y, Murakami Y, Matsuo K, Hamamoto R, Kohno T. Genomic Profiles of Pathogenic and Moderate-Penetrance Germline Variants Associated With Risk of Early-Onset Lung Adenocarcinoma. J Thorac Oncol 20, 1626–1638 (2025)

  15. Furukawa R, Tozaki T, Mizukami K, Iwasaki Y, Kawate K, Kikuchi M, Ishige T, Momozawa Y, Fukui E, Kakoi H. Mutation rate and spectrum of germline de novo mutations in a closed population of Thoroughbred horses. J Equine Vet Sci 154, 105682 (2025)

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