Related Experiment Video
Updated: Sep 30, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Transcriptional profiling reveals that several common fragile-site genes are downregulated in ovarian cancer
Stacy R Denison1, Nicole A Becker, Matthew J Ferber
1Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Abstract:
Previous transcriptional profiling analysis of 14 primary ovarian tumors identified approximately 12,000 genes as decreased in expression by at least twofold in one or more of the tumors sampled. Among those genes were several known to be mapped to common fragile sites (CFSs), some of which had previously been shown to exhibit a loss of expression in ovarian carcinoma. Therefore, we selected a subset of genes to determine whether they localized within CFSs. Of the 262 genes that were downregulated at least twofold in 13 of 14 tumors, 10 genes were selected based on the following criteria: localization to a CFS band; documented aberrations in at least one malignancy; and feasibility of scoring breakage at the specific CFS. Fluorescence in situ hybridization analysis was performed using bacterial artificial chromosome clones encompassing portions of the genes to determine the position of the genes relative to their corresponding CFSs. Nine genes were determined to localize within seven previously uncloned CFSs. Semiquantitative reverse-transcription/polymerase chain reaction analysis of the cell lines and primary ovarian tumors validated the downregulation of seven of the 10 genes. We identified portions of seven uncloned CFSs and provide data to suggest that several of the genes mapping within CFSs may be inactivated in ovarian cancer.
Insights
This study investigated gene expression in ovarian tumors, finding that several genes located in common fragile sites (CFSs) were downregulated. These findings suggest CFS genes may be inactivated in ovarian cancer, impacting tumor development.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Transcriptional profiling of ovarian tumors revealed widespread gene downregulation.
- Several downregulated genes were known to map to common fragile sites (CFSs).
- Some CFS genes previously showed reduced expression in ovarian carcinoma.
Purpose of the Study:
- To determine the localization of downregulated genes within CFSs.
- To investigate the potential inactivation of CFS genes in ovarian cancer.
- To identify novel CFS regions and associated genes.
Main Methods:
- Selection of 10 downregulated genes based on CFS localization, malignancy aberrations, and breakage feasibility.
- Fluorescence in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones to map gene positions relative to CFSs.
- Semiquantitative reverse-transcription/polymerase chain reaction (RT-PCR) to validate gene downregulation in cell lines and primary tumors.
Main Results:
- Nine of the 10 selected genes were localized to seven previously uncloned CFSs.
- Downregulation of seven of the 10 genes was validated by RT-PCR in ovarian samples.
- Identification of gene locations within seven novel CFS regions.
Conclusions:
- Several genes mapping to common fragile sites are downregulated in ovarian cancer.
- These findings suggest that genes within CFSs may be inactivated during ovarian tumorigenesis.
- The study identified novel CFS regions and provides insights into gene regulation in ovarian cancer.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:37Epigenetic Regulation
X-chromosome...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...