Gene associated with ovarian cancer identified
High-grade serious ovarian carcinoma (HGSOC) is the 7th most common cancer form. It ranks 8th for being the leading cause of deaths by cancer in women worldwide. Despite being a fatal malignancy, a little is known about the origin of the disease.
Recently, A new study by scientists at the College of Veterinary Medicine has pinpointed the specific genes responsible for drive or delay of this deadly cancer.
Senior author of the study, John Schimenti, said that an enormous genomic mutation data mined on cancer genetics have been considered and tried to predict its functional role. This study was published in Cell Reports on September 1.
Schimenti along with Alexander Nikitin, professor of pathology, director, Cornell Stem Cell Program, and members of the respective labs formed the team for the research to gain a better understanding of HGSOC.
In HGSOC, multiple genetic “hits” are responsible almost every time for the disease to occur. Generally, two or three hits are required and a single mutation alone is unlikely to turn a cell cancerous. The same cancer can be caused by different combinations of genes.
Once a key genome-destabilizing mutation occurs, other mutations follow to add to the complexity, said Schimenti. Sequenced tumors unleash a plethora of mutations. Some of these mutations are among the originator of cancer itself, while others are spinoffs.
The question regarding the distinction between the genetic drivers and the passengers in the disease has been a long-standing issue in cancer research, added Schimenti.
To analyze the malignancy sparking mutations, researchers wanted to test the possible combinations of genetic suspects. The researchers turned for help to the Cancer Genome Atlas, a global collaborative database of compiled genetic information from tumor samples of cancer patients and the mutated genes associated with them.
Twenty genes associated with HGSOC mutations were listed. They created random combinations of mutations in cells cultured from the surface of the ovary, including epithelial stem cells and regular epithelial cells with the help of CRISPR gene-editing technology. This helped the researchers to detect the cell types that are more likely to be susceptible to the mutations.
The combination of mutations associated with the particular group of cancerous cells was noted. This helped to figure the genes leading the process and the cell type in which cancer originated.
The study confirmed the suspects of the team of researchers. when hit with mutations, the ovarian stem cells were found to be more likely to become malignant. Unexpectedly, they also discovered the genes that had the opposite effect.
Schimenti said that in the study the various gene that helps along the process of turning the cells cancerous were found. Interestingly, they found that there was another type of gene with the opposite function. These genes when mutated inhibited the initiation of the cancer process.
The information about the cells of origin and the major genes involved in the initiation of this highly aggressive form of ovarian cancer can useful for ovarian and for other cancer in general. The screening method for cancer drivers used in this study can be used to study cancer occurring in the other organs of the body said Nikitin.
Patients with ovarian cancer who have biopsied their tumors and have the genetic data of the tumors cells are will be particularly benefitted the findings of the study, said Schimenti.
Schimenti added that previously, the mutated genes could be sorted but their possible role remained unknown, but now the important genes can be figured out. This will help to eventually develop drugs for the targeted genes causing the transformation in normal cells.
This study was funded by the Ovarian Cancer Research Fund, the National Institutes of Health, the National Institutes of Health, the New York State Stem Cell Science Program, and the National Cancer Institute.
Gene associated with ovarian cancer identified
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