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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Genome-wide DNA copy number analysis in clonally expanded human ovarian cancer cells with distinct invasive/migratory
Lei Li1, Huimin Bai1, Jiaxin Yang1
1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract:
Ovarian cancer has the worst prognosis of any gynecological malignancy, and generally presents with metastasis at advanced stages. Copy number variation (CNV) frequently contributes to the alteration of oncogenic drivers. In this study, we sought to identify genetic targets in heterogeneous clones from human ovarian cancers cells. We used array-based technology to systematically assess all the genes with CNVs in cell models clonally expanded from A2780 and SKOV3 ovarian cancer cell lines with distinct highly and minimally invasive/migratory capacities. We found that copy number alterations differed between matched highly and minimally invasive/migratory subclones, differentially affecting specific functional processes including immune response processes, DNA damage repair, cell cycle and cell proliferation. We also identified seven genes as strong candidates, including DDB1, ERCC1, ERCC2, PRPF19, BCAT1, CDKN1B and MARK4, by integrating the above data with gene expression and clinical outcome data. Thus, by determining the molecular signatures of heterogeneous invasive/migratory ovarian cancer cells, we identified genes that could be specifically targeted for the treatment and prognosis of advanced ovarian cancers.
Insights
This study identifies key genes altered by copy number variation (CNV) in ovarian cancer cells with different invasive abilities. These findings offer potential new targets for treating advanced ovarian cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Ovarian cancer presents a poor prognosis, often diagnosed at advanced metastatic stages.
- Copy number variation (CNV) is a significant factor in altering oncogenic drivers in cancer.
Purpose of the Study:
- To identify genetic targets within heterogeneous clones of human ovarian cancer cells.
- To investigate the role of CNVs in distinct invasive and migratory capacities of ovarian cancer cell sublines.
Main Methods:
- Utilized array-based technology to systematically assess CNVs in clonally expanded cell models (A2780 and SKOV3).
- Compared CNV profiles between highly and minimally invasive/migratory subclones.
- Integrated CNV data with gene expression and clinical outcome data.
Main Results:
- Identified distinct copy number alterations between invasive and non-invasive subclones.
- Observed differential effects of CNVs on immune response, DNA damage repair, cell cycle, and proliferation.
- Pinpointed seven candidate genes (DDB1, ERCC1, ERCC2, PRPF19, BCAT1, CDKN1B, MARK4) based on integrated analysis.
Conclusions:
- Molecular signatures of heterogeneous ovarian cancer cells reveal specific functional process alterations.
- Identified potential therapeutic and prognostic gene targets for advanced ovarian cancer treatment.

