Science Translational Medicine.
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.
(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
Hear Diaz discuss the research in this podcast, courtesy of the American Association for the Advancement of Science.
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
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
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.