However, differences in gene and protein expression are identified among GCT histologies

However, differences in gene and protein expression are identified among GCT histologies. and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/-catenin and TGF-/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. Introduction Classification of GCTs mOGCT epidemiology, treatment, and hormonal disturbances Survival and QOL after mOGCT diagnosis Gonadal and GCT development PXS-5153A Predisposition to GCT in the dysgenetic and phenotypically normal gonad Methods of the Review Genome Profiling of mOGCT DNA ploidy: image and flow cytometry analyses Chromosome G-banding analyses In situ hybridization: CGH and PXS-5153A 12p FISH analyses Polymorphic marker studies Transcriptome Profiling of mOGCT mRNA expression miRNA expression Biomarkers of mOGCT DNA methylation Protein expression and gene mutations Histology-specific molecular features of mOGCT Comparing Molecular Development of mOGCT and TGCT Concluding Remarks and Perspectives I. Introduction Neoplasms presenting in the ovary can originate from any of the various cell types present. The tumor may be derived from the surface epithelium, the stroma, or the cellular elements of the follicle, where the latter may result in sex PXS-5153A cord-stromal tumors (such as granulosa cell tumor or thecoma) or germ cell tumors (GCTs) (1, 2). The most frequently occurring ovarian GCTs are benign, cystic mature teratomas (MTs) that may show highly differentiated tissue and high morphological heterogeneity. This review focuses on the rare gonadal, malignant ovarian GCTs (mOGCTs), which occur predominantly in girls and young women and have not been as well studied as other ovarian tumors. Given the presumed common cell of origin in mOGCTs and their male counterpart, testicular GCTs (TGCTs), parallels between the molecular mechanisms of these 2 tumor types and the tumors of patients with disorders of sex PXS-5153A development (DSD) are discussed. By a crucial review and summarization of published data, the current knowledge of the molecular basis underlying mOGCT are presented. Specifically, the review summarizes genomic aberrations in mOGCTs as studied by ploidy, cytogenetic banding, comparative genomic hybridization (CGH) and microsatellite loci analysis, and genome-wide mRNA expression and microRNA (miRNA) expression studies as well as expression of single genes and proteins, including relevant mutational studies. Results from these 3 levels of molecular characterization are compared for concurrence and discussed in context of the pathogenesis of mOGCTs. A. Classification of GCTs Across both sexes, malignant GCTs most frequently occur in the gonads of young adult males as TGCTs, more rarely in the gonads of females (as OGCT) and infantile males, and most rarely at extragonadal sites such as the central nervous system, mediastinum, retroperitoneum, and coccyx (3). GCTs are also frequently observed in individuals with DSD (4), underlining the pathogenetic influence of disturbed gonadal development around the malignant transformation of germ cells. According to the World Health Business classification system, OGCTs are divided into 3 categories: primitive GCT, biphasic or triphasic teratoma, and monodermal teratoma and somatic-type tumors associated with dermoid cysts (5, 6). The common benign mature cystic teratomas belong to the subgroup of the biphasic and triphasic teratomas, and the remaining OGCTs are malignant. The primitive GCTs are subdivided into dysgerminoma (DG), the Rabbit Polyclonal to USP32 ovarian counterpart of the male testicular seminoma, and non-DGs: yolk sac tumor (YST), also known as endodermal sinus tumor, embryonal carcinoma (EC), polyembryoma, nongestational choriocarcinoma (CC), and mixed GCT containing various histologies, including immature teratoma (IT). The most common mOGCT histologies are the DG followed by YST. Pure EC is usually relatively rare, and this component of mOGCT should be distinguished from stem-cell/EC-like cells occasionally found in association with epithelial ovarian cancer (within the tumor or in malignant ascites) and often defined as a side populace of tumor-initiating cells (7, 8). mOGCTs are staged according to the International Federation of Gynaecology and Obstetrics (FIGO) classification (9). The mOGCTs are believed to be derived from primordial germ cells (PGCs), where the pluripotency characteristics they retain facilitate the potential to differentiate into the spectrum of histological PXS-5153A subtypes listed above. The development of non-DGs is usually characterized by differentiation of these cells into histologies that mimic embryonic and extraembryonic tissues. The mOGCTs have earlier.