An international team of scientists has achieved a breakthrough by finding the genetic cause of a very rare and aggressive type of ovarian cancer that most often strikes girls and young women.

The study, led by Translational Genomics Research Institute (TGen) a non-profit organization based in Phoenix, AZ, is published in the journal Nature Genetics.

The researchers say their finding, discovered by groundbreaking work in genomics, reveals many strong links between a mutation in a gene called SMARCA4 and an overwhelming majority of patients with a rare and aggressive form of ovarian cancer known as small cell carcinoma of the ovary, hypercalcemic type (SCCOHT).

The researchers write:

“We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.”

Dr. Jeffrey Trent, president and research director of TGen and senior author of the study, explains why their findings are so remarkable:

Many genetic anomalies can be like a one-lane road to cancer; difficult to negotiate. But these findings indicate a genetic superhighway that leads right to this highly aggressive disease. The correlation between mutations in SMARCA4 and the development of SCCOHT is simply unmistakable.”

Ovarian cancer is the fifth leading cause of cancer death among American women. Like many other ovarian cancer types, SCCOHT is often not diagnosed until it is already in an advanced stage. Chemotherapy evokes no response and nearly two thirds of patients do not survive more than 2 years after diagnosis.

The average age at which SCCOHT strikes is 24 years, ranging from baby girls as young as 14 months to women aged 58. The youngest patient in this study was 9 years old.

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Researchers found genetic mutations in a gene called SMARCA4 are linked to development of a rare ovarian cancer.

The researchers believe the breakthrough could lead to new cancer treatments not only of this very rare cancer, but also of other types. The SMARCA4 gene is already known to be linked to cancers of the lung, brain and pancreas.

Dr. Bert Vogelstein, director of the Ludwig Center at Johns Hopkins University and a pioneer of cancer genomics who was not involved in the study but who has examined the results very closely, describes the findings as “a landmark in the field.”

“The work identifies SMARCA4 mutations as the culprit, and most future research on this disease will be based on this remarkable discovery,” says Dr. Vogelstein, who is also an Investigator at the Howard Hughes Medical Institute.

Lead author Pilar Ramos, a research associate with TGen, adds:

We set out to uncover any small sliver of hope for women afflicted with this rare cancer. What we found instead are the nearly universal underpinnings of SCCOHT. By definitively identifying the relationship between SMARCA4 and SCCOHT, we have high confidence that we have set the stage for clinical trials that could provide patients with immediate benefit.”

TGen say much of the work behind the study was inspired by the memory of one of their patients, 22-year-old Taryn Ritchey who died from SCCOHT in 2007. Her mother Judy Jost of Cave Creek, AZ, says her daughter never gave up, and she would have been “incredibly excited” by the new study and glad that it might help other young women like herself.

Support for the study came from many sources, including the Marsha Rivkin Center for Ovarian Cancer Research, the Anne Rita Monahan Foundation, the Ovarian Cancer Alliance of Arizona and the Small Cell Ovarian Cancer Foundation.

Medical News Today recently reported on a study that found inherited gene mutations in 20% of women with ovarian cancer. Researchers who studied ovarian cancer patients with no known family history of the disease found 1 in 5 had inherited alterations in genes known to be linked to ovarian and breast cancer.