Understanding the Biology of Solid Tumors with Multi-omics Approaches

With the rapid advancement of sequencing technologies, the amount of genomic data generated has increased dramatically. Analyzing such large datasets requires advanced bioinformatics approaches. Leveraging our expertise in bioinformatics, we collaborate with various research groups to explore the pathogenesis of a wide range of solid cancers, not limited to brain tumors but also encompassing urological and gastrointestinal malignancies. Our laboratory has been involved in numerous studies, from next-generation sequencing analysis to prognosis prediction, and has contributed to the molecular understanding of various solid tumors.

Selected Genomic Studies Beyond Brain Tumors:

• Fujii Y, Sato Y, Suzuki H, et al. Molecular classification and diagnostics of upper urinary tract urothelial carcinoma. Cancer Cell. 2021; 39(6):793?809.
• Yokoyama A, et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 2019; 565(7739):312?317.
• Sato Y, et al. Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. Science. 2014; 344(6186):917?920.
• Sato Y, et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nature Genetics. 2013; 45(8):860?867.

Epigenomic Analysis and Novel Therapeutic Targets in Upper Urinary Tract Urothelial Carcinoma

In collaboration with the Department of Urology at the University of Tokyo, we have conducted comprehensive analyses of over 200 urothelial carcinoma cases. These studies have revealed the landscape of genetic alterations, gene expression profiles, and DNA methylation patterns, leading to a proposed molecular classification of urothelial carcinoma.

Recent findings suggest that alterations in genes related to epigenomic regulation are frequent in urothelial carcinoma. Building upon these findings, our ongoing work includes in-depth epigenomic analyses and single-cell sequencing to uncover disease mechanisms and identify novel therapeutic targets for personalized medicine.

Structural Alterations in MYC/PVT1 and Oncogenic circRNAs Across Solid Tumors

Through collaboration with the Bagchi Laboratory at Sanford Burnham Prebys, we discovered that chromosomal rearrangements in the MYC/PVT1 locus are common across a broad spectrum of cancers. Notably, structural alterations in PVT1 are clustered in specific regions.

By analyzing whole-genome sequencing data from over 2,000 tumor samples, we identified recurrent structural variants that generate novel circular RNAs (circRNAs). These circRNAs appear to function as oncogenes that promote tumorigenesis.
(Ashutosh Tiwari et al., bioRxiv, 2025)

Our findings suggest that MYC/PVT1 structural alterations and their resulting oncogenic circRNAs play a pivotal role in cancer development and represent promising targets for future therapies.

Genomic Analysis and Tumorigenesis in Retinoblastoma

In collaboration with the Pei Laboratory at Children’s National Hospital, we are analyzing whole-genome sequencing data from retinoblastoma patients. Beyond the well-known RB1 gene mutations, this project aims to uncover novel genetic alterations involved in tumor development.

Utilizing a retinoblastoma mouse model developed by the Pei Lab, we perform comprehensive sequencing to investigate the tumor’s molecular mechanisms. These studies aim to deepen our understanding of retinoblastoma tumorigenesis and contribute to the development of new therapeutic strategies.