Ovarian cancer DNA may hold clues to disease's progression

July 26, 2013 | by Tami Dennis

Ovarian cancer is complex, difficult to diagnose early and often fatal. If researchers could better understand what promotes progression of the disease, however, they might also understand how to better intervene, improving a patient’s chances of survival.

DNA molecule DNA replication is crucial to cell replication. Now it appears that, in ovarian cancer, DNA replication actually encourages other DNA errors.

New research provides some clues. In a study published this week in the journal Gynecologic Oncology, researcher Linda Malkas, Ph.D., deputy director of basic research at City of Hope, and colleagues at Indiana University shed some light on the genetic instability of ovarian cancer itself.

Already they knew that high rates of genetic instability within ovarian cancer cells were linked to poor overall survival in patients. Now they’ve found that the DNA replication of ovarian cancer cells actually encourages other DNA errors, which could in turn lead to altered properties of these cancer cells.

We asked Malkas three key questions about her research:

What was the main finding of this study? We found that ovarian cancer cells harbor a mutagenic DNA replication apparatus that produces significantly more nucleotide errors in nascent DNA than it does in nonmalignant ovarian cells. The penchant of the ovarian cancer DNA replication apparatus for generating single nucleotide errors was further demonstrated by the observation that there is a difference in the efficiency with which the DNA polymerases – from both nonmalignant ovarian surface epithelial cells and ovarian cancer cells – create specific types of nucleotide mismatches during DNA synthesis.

What’s the significance of the finding? Our results – showing that the DNA replication apparatus of ovarian cancer cells bears a propensity for carrying out a process of DNA synthesis that is error-promoting compared to that of nonmalignant ovarian cells – could potentially explain the origin of some of the elevated frequency of spontaneous random mutations observed in ovarian tumors.

What’s next in this line of research? The systematic analysis of the DNA replication process in ovarian cancer could uncover information on some of the molecular mechanisms that drive the accumulation of genetic damage, and probably contribute to the pathogenesis of the disease.

In other words, the more researchers know about the disease, and its progression, the better positioned they are to fight it.

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number P30CA033572.  The content is solely the responsibility of the authors and does not necessarily represent that official views of the National Institutes of Health. The National Institutes of Health/National Cancer Institute and the Ovarian Cancer Research Foundation also supported this work.


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