标题:
Genome-wide DNA copy number analysis in clonally expanded human ovarian cancer cells with distinct invasive/migratory capacities
讲者:
Lei
单位:
北京协和医院
播放:
5746
论文摘要:
Abstract
Objective: 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. The aim of this study was to identify molecular targets in the heterogeneous clones of human ovarian cancer cells for the treatment of advanced ovarian cancers.
Method: 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. Data regarding candidate genes identified via functional enrichment and viability screens were integrated with clinical data to determine the outcomes associated with unbalanced gene alterations and gene overexpression in patients with high-grade serous ovarian cancer.
Results: 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.
Conclusion: 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.