An international team led by the Translational Genomics Research Institute (TGen) reports discovering the cause of a rare type of ovarian cancer that most often impacts girls and young woman. The study (“Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4”) is published online in Nature Genetics.
The findings revealed a “genetic superhighway” mutation in a gene found in the overwhelming majority of patients with small cell carcinoma of the ovary, hypercalcemic type, also known as SCCOHT, according to Jeffrey Trent, Ph.D., president and research director or TGen and senior author of the study. This type of cancer usually is not diagnosed until it is in its advanced stages and does not respond to standard chemotherapy. Sixty-five percent of patients die within two years. It has affected girls as young as 14 months, and women as old as 58 years—with a mean age of only 24 years old. In this study, the youngest patient was nine years old.
“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,” wrote the investigators. “These data implicate SMARCA4 in SCCOHT oncogenesis.”
According to Dr. Trent, “The correlation between mutations in SMARCA4 and the development of SCCOHT is simply unmistakable.” He added that, while the breakthrough is for a relatively rare cancer, discovering the origins of this type of ovarian cancer could have implications for more common diseases.
The SMARCA4 gene, which was previously associated with lung, brain, and pancreatic cancer, was the only recurrently mutated gene in the study's samples. The implications of this discovery, therefore, may be widespread.
“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,” said Pilar Ramos, a TGen research associate and the study's lead author. “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.”