Global dysregulation of the chromosome 14q32 imprinted region in uterine carcinosarcoma

Uterine carcinosarcoma (UCS) is a rare but very aggressive cancer of the female reproductive tract with an extremely poor prognosis. With the goal of understanding the role of microRNA (miRNA) dysregulation in these tumors, we profiled the expression of 667 human miRNAs in a panel of eight UCS patients and five benign control primary tissue samples. These expression profiles revealed two important characteristics of UCS. First, compared with the two most common uterine cancers, endometrial endometrioid adenocarcinoma and endometrial serous adenocarcinoma, UCS samples display a virtually unique pattern of miRNA dysregulation with an overlap of only 5% among the three tumor types. In addition, nearly one-third of the miRNAs significantly dysregulated in UCS tissues compared with benign endometrium (32 of 114) lie in a single small (250-kb) imprinted region of chromosome 14q32. These data suggest that the presence of such a global, region-specific disruption substantially contributes to the unique histology and poor outcome of this type of cancer.