Carcinosarcomas are rare, highly aggressive tumors associated with very poor outcomes. Recently, researchers at Yale University School of Medicine shed light on the genetic signature of uterine and ovarian carcinosarcomas, which could influence the development of better treatments.

The study, “Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition,” was published in Proceeding of the National Academy of Sciences (PNAS).

Endometrial and ovarian cancers are the most prevalent gynecologic tumors in women with an estimated 82,330 new cases per year in the United States alone, according to the National Cancer Institute. This year, the NIS predicts that the cancers could lead to 24,710 deaths. Although carcinosarcomas represent only 2 to 5 percent of all gynecologic cancers, and 1 to 2 percent of ovarian cancers, its high biologic aggressiveness and resistance to standard chemotherapy and radiation therapies lead to the disproportionate number of deaths.

Carcinosarcomas are characterized by having features of carcinoma (common of epithelial cancers like breast, lung, or prostate), and sarcoma (observed in blood cancers and bone or muscle cancers). Given poor prognosis and lack of consensus regarding the origin of the cancers, the Yale researchers sought to examine the genetic landscape of carcinosarcomas with hope to determine the molecular basis of the tumor’s aggressive behavior and to identify new therapeutic targets.

Using extensive genomic analysis, the team identified critical mutations for tumor development. They also examined copy number variations — which are genes that are not mutated but highly expressed, giving the tumors a growth advantage over normal tissue.

“In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas, we found an excess of mutations in genes encoding specific groups of proteins, which may potentially explain their mixed tissue characteristics,” senior author Dr. Alessandro Santin, professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, and head of the gynecological cancers research program at Smilow Cancer Hospital at Yale-New Haven, said in a press release.

Researchers also identified the origin of the carcinosarcomas.

“We’ve established unequivocally the common genetic origin of these tumors as epithelial tumors,” Santin added. “Importantly, by studying the genetics of both the carcinomatous and sarcomatous elements of these tumors, we demonstrated that the transition from carcinoma to sarcoma, which represent one of the main characteristics of these tumors, may happen at different times during the evolution of these cancers.”