Release date: 2015-02-03
Ovarian clear cell carcinoma (OCCC) is a highly malignant type of ovarian cancer that is not sensitive to chemotherapy and has a poor prognosis. Recently, a group of researchers at the University of North Carolina School of Medicine in the United States found two important genes ARID1A and PIK3CA that occur in OCCC. When these two genes are simultaneously mutated, the incidence of OCCC is 100%. This study was published in the most recent issue.
Based on the results of previous cancer genome sequencing, researchers have known that ARID1A is a tumor suppressor gene for many tumors, including OCCC, and has a high mutation rate in OCCC. However, recent studies have found that ARID1A alone is not sufficient to cause OCCC production unless there is another overexpression of PIK3CA, a gene encoding the phosphoinositide 3-kinase catalytic subunit. After silencing ARID1A in mice and simultaneously activating PIK3CA, the mice developed highly permeable tumors, similar to the pathological type of OCCC, with blood-type ascites, and the final survival period did not exceed 7.5 weeks. The researchers then tested a PI3K inhibitor BKM120 in mice and found that tumor growth was inhibited and the survival of the mice was significantly prolonged. The researchers said that the PIK3CA gene mutation is like a catalyst for controlling cell growth, and combined with the ARID1A mutation, it can accelerate the cancer-promoting effect.
But why do two mutations combine to produce 100% carcinogenic effects? The team found a key factor in the interleukin-6 (IL-6) involved in this process. Mutation of ARID1A and PIK3CA resulted in overproduction of IL-6. In general, IL-6 mainly mediates cellular signaling involved in the inflammatory response, but it is not clear whether it has a role in tumors. But researchers speculate that IL-6 can promote the development of OCCC and may lead to death. ARID1A, as a tumor suppressor gene, inhibits this effect.
In summary, determining the role of ARID1A and PIK3CA mutations in the development of OCCC can help to investigate new ovarian cancer drugs in the future, and is more likely to be a new tumor marker for early OCCC screening or prevention.
Source: Bio Valley
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