Friday, 11 January 2013

Johns Hopkins Scientists Use Pap Test Fluid To Detect Ovarian, Endometrial Cancers

Using cervical fluid obtained during routine Pap tests, scientists at the Johns Hopkins Kimmel Cancer Center have developed a test to detect ovarian and endometrial cancers. In a pilot study, the “PapGene” test, which relies on genomic sequencing of cancer-specific mutations, accurately detected all 24 (100 percent) endometrial cancers and nine of 22 (41 percent) ovarian cancers. Results of the experiments are published in the Jan. 9 issue of the journal Science Translational Medicine.
The investigators note that larger-scale studies are needed before clinical implementation can begin, but they believe the test has the potential to pioneer genomic-based cancer screening tests.
The Papanicolaou (Pap) test, during which cells collected from the cervix are examined for microscopic signs of cancer, is widely and successfully used to screen for cervical cancers. However, no routine screening method is available for ovarian or endometrial cancers.
Since the Pap test occasionally contains cells shed from the ovaries or endometrium, cancer cells arising from these organs could be present in the fluid as well, says Luis Diaz, M.D., associate professor of oncology at Johns Hopkins, as well as director of translational medicine at the Ludwig Center for Cancer Genetics and Therapeutics and director of the Swim Across America Laboratory, also at Johns Hopkins. The laboratory is sponsored by a volunteer organization that raises funds for cancer research through swim events. “Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost-effective way,” adds Diaz.
Hear Diaz discuss the research in this podcast, courtesy of the American Association for the Advancement of Science.
Cervical fluid of patients with gynecologic cancer carries normal cellular DNA mixed together with DNA from cancer cells, according to the investigators. The investigators’ task was to use genomic sequencing to distinguish cancerous from normal DNA.
The scientists had to determine the most common genetic changes in ovarian and endometrial cancers in order to prioritize which genomic regions to include in their test. They searched publicly available genome-wide studies of ovarian cancer, including those done by other Johns Hopkins investigators, to find mutations specific to ovarian cancer. Such genome-wide studies were not available for the most common type of endometrial cancer, so they conducted genome-wide sequencing studies on 22 of these endometrial cancers.
From the ovarian and endometrial cancer genome data, the Johns Hopkins-led team identified 12 of the most frequently mutated genes in both cancers and developed the PapGene test with this insight in mind.
The investigators then applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital, Memorial Sloan-Kettering Cancer Center, the University of São Paulo in Brazil and ILSbio, a tissue bank. The new test detected both early- and late-stage disease in the endometrial and ovarian cancers tested. No healthy women in the control group were misclassified as having cancer.

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