July 01, 2011
By Donna Peck
Researchers analyzing the genetic makeup of ovarian cancer tumors have discovered several gene mutations that may play a key role in driving the cancer. The findings could eventually lead to tests for earlier diagnosis and to better treatment. Ovarian cancer kills nearly 14,000 women in the United States each year. It's usually not spotted until at an advanced stage.
The gene sequencing was carried out by the Cancer G enome Atlas (TCGA), a federally funded network of medical centers that studied high-grade serious ovarian adenocarcinoma (HGS-OvCA), analyzing 316 tumors. One of the researchers on the project is Andrew K. Godwin, PhD, who participated in the study while he was at Fox Chase Cancer Center in Philadelphia, Pa., where he was director of the Clinical Molecular Genetics Laboratory, the co-leader of the Women's Cancer Program, and the initiator and director of one of the top biospecimen repositories in the country. Last October, Godwin joined The University of Kansas Cancer Center, where he is now associate director for translational research and director of molecular oncology at the University of Kansas Medical Center.
Among the main findings:
Abnormalities in a key gene, called TP53, were found in nearly all (96 percent) of patients diagnosed with these tumors.
Based on the genetic scan, there appear to be four different subtypes of HGS-OvCa, as well as four additional related subtypes.
A little more than one in every five of the tumors had mutations in the BRCA1 and BRCA2 genes, which have long been linked to risks for both ovarian and breast cancers. In this case, patients whose cancers carried these mutations had better survival rates than those who did not.
Overall, specific patterns in 108 genes were also linked to poorer survival, while those for another 85 genes were linked to better outcomes. Patients with genetic activity deemed "poor" were found to have 23 percent shorter survival than those without such genetic aberrations.
Godwin says the findings validate what many cancer researchers already suspected: not all ovarian tumors are alike. "The molecular changes that occur in one case of ovarian cancer can be dramatically different from that of another when you look at what's gone wrong in cell growth and death."
Godwin says the Cancer Genome Atlas work is increasing the potential for personalized cancer medicine, in which all tumors are not treated in the same way. "We are getting closer to the time when we can now look at an individual tumor, characterize the genetic alterations that have caused that cancer to occur, and use targeted therapies for treating that particular cancer."
The research was published in Thursday''s issue of the journal Nature.