A research team led by investigators at NYU Langone Medical Center's Perlmutter Cancer Center and The University of Texas MD Anderson Cancer Center have managed to chart the complex molecular biology of uterine carcinosarcoma (UCS), a rare and aggressive gynecologic cancer. Findings from this new study, published recently in Cancer Cell through an article entitled “Integrated Molecular Characterization of Uterine Carcinosarcoma,” should supply physicians with a new collection of genomic information that allows them to better determine the specific genetic fingerprint of each patient's tumor and to find treatment options that better suit them.
The researchers found that while all UCS tumors share some genetic traits, there is great diversity among the tumors. Instead of having a few commonly mutated genes, UCS tumors were found to have alterations in genes that play a wider variety of roles in cancer biology than previously thought. Thus, anti-cancer drugs, which work against specific genetic targets, are more likely to be effective against certain UCS tumors, but not against others, due to the large variation in mutations. Additionally, the study traced the molecular roots of UCS using genomic, epigenetic, transcriptomic, and proteomic analyses to create a more comprehensive genetic atlas for the disease.
“The biggest surprise was the genetic variety within tumors of this type,” explained co-senior study investigator Douglas Levine, M.D., director of the division of gynecologic oncology at the Perlmutter Cancer Center. Dr. Levine added that the finding helps explain why UCS has been especially difficult to treat. However, it also points doctors toward possible treatments, some already approved and others current in clinical studies.
The current study utilized tissue samples from 57 women with confirmed cases of UCS. Of the 57 women sampled, 64 percent had the cancer recur within the study follow-up period, and 58 percent died—underscoring the urgency for new treatment options as only about one out of every three women survives longer than five years after diagnosis with UCS. The average follow-up period in the study was 25.7 months.
Upon analysis of the 57 samples, investigators found 60,000 individual characteristics, which were narrowed down to 9,149 genetic mutations. Based on this information, clinical data about UCS, and studies of other related cancers, the team identified five genes most commonly associated with UCS. Interestingly, one gene that normally protects against cancer—P53—was mutated in 91 percent of the tumors in the study.
After an intensive molecular analysis of the tissue samples, the team also compared the UCS sample to data on other cancers in The Cancer Genome Atlas of the National Cancer Institute and the National Human Genome Research Institute. The Cancer Genome Atlas is a central repository of genomic data gleaned from tissue samples from more than 11,000 people, providing reference details on 33 different cancers.
Comparing traits of UCS tumors to these large databases has revealed that UCS may be related at the molecular level to entirely different kinds of cancer. Even though that means treating UCS remains difficult, this discovery could be good news for patients and their doctors. “Now, we can apply what we've learned to create more specific clinical trials,” Dr. Levine concluded.