hum0030-v6Release info

The Molecular Biological Analysis about Occurrence and Malignant Transformation in gynecological carcinogenesis

Aims

To clarify the biological difference between clear cell carcinoma and other histological subtypes in ovarian carcinomas by comparing copy number variants, and to identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing and RNA-sequencing. Then, characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes, and prognostic factors and effectiveness of PARP inhibitor. Based on the results of whole-exome sequencing, an investigator-initiated, phase 2 clinical trial will be conducted to evaluate the efficacy and safety of the PARP inhibitor olaparib in HRD-positive cases.
Understanding the immune regulatory mechanisms in endometrial cancer is crucial for improving immunotherapy strategies. To elucidate the relationship between the tumor immune microenvironment and HLA class I expression, with a particular focus on their impact on CD8+ T cell infiltration patterns. By investigating the molecular basis of immune evasion across different histological and molecular subtypes, we will generate evidence that will contribute to the development of personalized immunotherapy strategies.
Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial malignancy in which carcinomatous and sarcomatous components coexist within the same tumor. Using integrated microdissection-based bulk RNA sequencing and Xenium spatial transcriptomics, we profiled over one million cells across eight UCS cases to elucidate the spatial organization of epithelial-mesenchymal transition (EMT), the carcinoma-to-sarcoma differentiation trajectory, EMT-intermediate cellular states, and the relationship between EMT and the tumor immune microenvironment. These findings aim to clarify the mechanisms of tumor plasticity and cellular-state transition in uterine carcinosarcoma.

Methods

Copy Number Variation Analysis: Gene Chip Human Mapping 250K Nsp Arrays were used for detecting the signal intensity of about 260 thousands SNPs and intensities of ovarian clear cell carcinoma were compared to the ones of non-carcinoma.
Whole Exome sequencing and RNA-seq
Methylation array and Expression array
Target bisulfite sequencing
Xenium in situ spatial transcriptome analysis

Participants/materials

Ovarian cancer: 57 cases (12 endometrioid carcinoma) + 111 cases + 31 + 189 cases, Endometrial cancer: 86 cases, Uterine carcinosarcoma: 8 cases

URL

N/A

Principal investigator

Katsutoshi Oda

Affiliation

Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo

No research projects.