Evidence map›Paper›PMID 42087217›Full record

ArticleGenome medicine2026

Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.

Yong Wu, Xinyi Guo, Tiantian Wang, Tianyi Zhao, Siyu Chen, Ying Su, Qin Li, Jun Zhu, Lingfang Xia, Xingzhu Ju and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Yong Wu *Department of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Xinyi Guo *Department of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Tiantian Wang *Department of Biophysics, College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, China.
Tianyi Zhao *Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Siyu ChenDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Ying SuDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Qin LiDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Jun ZhuDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Lingfang XiaDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Xingzhu JuDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China.
Xiaohua WuDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China. wu.xh@fudan.edu.cn.
Shenglin HuangDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China. slhuang@fudan.edu.cn.
Zhixiang HuDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China. zhixiang_hu@fudan.edu.cn.
Xiaojun ChenDepartment of Gynecologic Oncology, Shanghai Key Laboratory of Medical Epigenetics, International Co- laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, 305 Rm., 7# Bldg., 270 Dong An Rd, Shanghai, 200032, China. doccxj2020@163.com.

Funding

National Natural Science Foundation of China 82002747Natural Science Foundation of Shanghai Municipality 24ZR1412100Shanghai "Rising Stars of Medical Talents" Youth Development Program WJWRC202310the Foundation of Shanghai Municipal Health Bureau 20224Y0233
6 · The paper itself

Abstract

backgroundOvarian clear cell carcinoma (OCCC) is a rare aggressive, and chemo-resistant subtype of epithelial ovarian cancer. Current limitations in precisely characterizing its molecular features have resulted in restricted availability of clinical targeted therapies and significant therapeutic challenges.

methodsTo address this unmet need, we conducted an integrative multi-omics study of 82 OCCC cases, incorporating whole-exome sequencing (WES), bulk RNA sequencing, and single-cell RNA sequencing (scRNA-seq).

resultsOur analysis uncovered recurrent mutations in multiple epigenetic regulators including ARID1A, EP300, and SETD2B, reinforcing chromatin remodeling as a hallmark of OCCC pathogenesis. Strikingly, FOXA2 mutations were absent in early-stage tumors but specifically enriched in advanced-stage cases (19% frequency), with functional validation demonstrating their role in driving malignant progression. Copy number alteration profiling revealed frequent amplifications in chromosomal arms such as 17q, which contains the ERBB2 oncogene that potentially regulates OCCC progression. Chromosomal translocations were detected in 35.59% of cases, including a novel FGFR2/RPAP3 fusion with therapeutic implications. Notably, scRNA-seq delineated immune-rich subsets characterized by abundant cytotoxic T-cell and B-cell infiltration, suggesting immunotherapeutic opportunities in a patient subset. Moreover, molecular subtyping identified ERBB2 amplification/overexpression as a high-risk feature strongly associated with poor survival. Patient-derived xenograft (PDX) models and a retrospective analysis of two clinical cases demonstrated that HER2-targeted antibody-drug conjugates (HER2-ADCs) significantly suppressed tumor growth and progression in OCCC patients with HER2 expression.

conclusionsIn summary, our study establishes the comprehensive molecular atlas and a targeted therapeutic subtyping framework, revealing therapeutic vulnerabilities and providing novel insights for advancing precision oncology in OCCC management.

Indexed as

Adenocarcinoma, Clear CellOvarian NeoplasmsAnimalsDNA Copy Number VariationsEpigenesis, GeneticExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMutationHER2-ADCOCCCtarget therapytherapeutic vulnerabilities

Identifiers

PMID42087217
PMCPMC13312614

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.