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Germ Cell Tumors of the Central Nervous System
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Matthew J. Murray, Ute Bartels, James C. Nicholson
At a transcriptomic level, histological subtypes of GCT display distinct gene expression profiles and patterns of cellular pathway activation.36,37 For example, germinomas express pluripotency genes (NANOG, POU5F1 (OCT3/4), TFAP2C, and UTF)37 whereas YSTs express genes relevant to differentiation (KRT8, KRT19) and lipid metabolism (APOA1, APOA2).37 In addition, YSTs/NGGCTs have activation of the BMP/Wnt38 and EGFR/mTOR39 proliferation pathways. These biological variances may account for differences in the observed natural history between germinomas and NGGCTs.
Familial Testicular Germ Cell Tumor
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Immunohistochemical markers for TGCT consist of PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C), LIN28, etc., which are expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells. Other diagnostic markers include HMGA1, HMGA2, kinase Aurora-B (which is present in IGCNU, seminomas, and embryonal carcinomas but not in teratomas and YST) [50,51].
New knowledge about adenomyosis
Published in Carlos Simón, Linda C. Giudice, The Endometrial Factor, 2017
Giuseppe Benagiano, Beatrice Ermini, Marwan Habiba, Ivo Brosens
Using Illumina® HT-12 v3 Expression BeadChip gene expression analysis, Mehasseb et al. (79) reported that Wnt5a was consistently downregulated in both the inner and the outer myometrium during both the secretory and the proliferative phases of the cycles. The top five downregulated genes in the inner myometrium of adenomyotic uteri (compared with controls), in the proliferative phase, were ELMO/CED-12 domain containing 1 (ELMOD1), forkhead box L2 (FOXL2), SH3 domain GRB2-like 3 (SH3GL3), FLJ43329 protein (LOC401089), and transcription factor AP-2 gamma (activating enhancer binding protein 2 gamma) (TFAP2C). The top five upregulated genes in the inner myometrium of adenomyotic uteri (compared with controls), in the proliferative phase, were immunoglobulin superfamily, member 10 (IGSF10); Fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor) (FLT1); SH3 and cysteine-rich domain (STAC); p300/CBP-associated factor (PCAF); and parathyroid hormone 2 receptor (PTH2R). The top five downregulated genes in the inner myometrium of adenomyotic uteri (compared with controls), in the secretory phase, were solute carrier family 3 (cystine, dibasic, and neutral amino acid transporters, activator of cystine, dibasic, and neutral amino acid transport), member 1 (SLC3A1); keratin 86 (KRT86); forkhead box Q1 (FOXQ1); tektin 1 (TEKT1); and prominin 1 (PROM1). The top five upregulated genes in the inner myometrium of adenomyotic uteri (compared with controls), in the secretory phase, were gliomedin (GLDN), peripherin (PRPH), mohawk homeobox (MKX), peptidase inhibitor 16 (PI16), and myotilin (MYOT) (80).
KCTD1 and Scalp-Ear-Nipple (‘Finlay–Marks’) syndrome may be associated with myopia and Thin basement membrane nephropathy through an effect on the collagen IV α3 and α4 chains
Published in Ophthalmic Genetics, 2023
Dongmao Wang, Paul Trevillian, Stephen May, Peter Diakumis, Yanyan Wang, Deb Colville, Melanie Bahlo, Una Greferath, Erica Fletcher, Barbara Young, Heather G. Mack, Judy Savige
KCTD1 is a transcriptional repressor or activator of TFAP2α, TFAP2β, and TFAP2γ (10). Mutations in the TFAP2 genes inform our understanding of the mechanisms underlying KCTD1 mutations. TFAP2A mutations result in the Branchio-Oculo-Facial syndrome (OMIM 113,620), with branchial and periauricular skin defects, and sometimes microophthalmia or anopthalmia, coloboma, hypertelorism, cleft lip, cleft palate, prominent ears, and hearing loss (11). Renal cysts and aplasia may occur. Mutations in the TFAP2B gene result in Char syndrome (12) (OMIM 169,100), with facial abnormalities, patent ductus arteriosus, and aplasia/hypoplasia of the fifth finger middle phalanges (13) together with hearing loss, multiple nipples (14), syndactyly (15,16), and sometimes myopia (17), strabismus (squint) (17) and coloboma. There may be supernumerary nipples (14), and absent second and third molar teeth (17,18). Mice with a targeted loss of Tfap2β have multiple renal cysts (19). The effects of TFAP2C on apoptosis and Wnt signalling may also contribute to kidney cyst formation (20).
Association of genetic variants in PDGFRA with high myopia in the Han population of southwestern China
Published in Ophthalmic Genetics, 2022
Lingxi Jiang, Guo Huang, Chao Dai, Rui Zheng, Chunbao Xie, Suyang Duan, Ling Zhong, Xiaoqi Liu, Bo Gong, Dezhong Yao, Zhenglin Yang, Yi Shi
Rs2114039 can be located in the transcription factor-binding sites of EZH2 and TFAP2C. EZH2 is PRC’s2 (Polycomb Repressor Complex2) catalytic core protein, which catalyzes H3K27 (Trimethylation of Histone H3 lysine 27) and mediates gene silencing of the targeted issues (25). Furthermore, EZH2 plays a crucial role in maintaining photoreceptors’ function (25) and regulates the processes of retinal progenitor proliferation (26). TFAP2C, which is an essential transcription factor, is expressed in postmitotic developing amacrine cells in mouse retinas and reveals a redundant requirement in horizontal and amacrine cell development (27). Generally, EZH2/TFAP2C and visual development have a strong correlation. However, rs6554162, rs7668190, and rs486450 are only located in EZH2’s transcription factor-binding sites. Four SNPs (rs2114039, rs6554162, rs7668190, and rs4864504) have an association with EZH2, potentially indicating that the correlation between transcription factors EZH2 and PDGFRA is of greater significance. This suggests that rs2114039 is likely to influence eye development through the EZH2 transcription factor-binding site and cause eye disorders, including HM. In addition, the results of this study present more possible directions of research for HM development.
Differential Activation of Immune Effector Processes in Mature Compared to Immature Sacrococcygeal Teratomas
Published in Fetal and Pediatric Pathology, 2022
Mette Hambraeus, Jenny Karlsson, Ioanna Kasselaki, Catharina Hagerling, Lars Hagander, David Gisselsson
It has been suggested that SCTs derive from primordial germ cells (PGCs), which are thought to arise in the fetal epiblast during the second week of gestation [7,20]. From week 3-4 of gestation, PGCs have been observed in the yolk sac wall, and from here they migrate through the hindgut to the genital ridges, which marks the end of the PGC stage [20]. In line with previous studies [9], our results show a high expression of certain genes involved in early germ cell differentiation and pluripotency. The transcription profile was found across all histological subtypes. Compared to the reference group of tumors, SCTs showed a high expression of SOX2, which encodes a protein required for stem-cell maintenance in central nervous tissue. This protein combines with OCT4 to form a transcription factor that controls a number of genes required for embryological development [21]. We also found increased expression of genes normally active in early germ cell development, i.e. PRMD1, TFAP2C, and KIT [19]. SOX2 regulates KIT-expression in PGCs and is essential for survival and continued proliferation [22]. The transcriptional regulator PRMD1 (BLIMP1) is a signature gene for germ cell-commitment in active migratory and gonadal PGCs [20]. It induces TFAP2C, which further regulates germ cell specific genes and inhibits somatic differentiation [23]. PRDM1, TFAP2C and KIT are regulators of hematopoietic stem cells, antibody secreting plasma cells and formation of the placenta, and may therefore be expressed throughout fetal development [24–26]. However, the combined expression is generally considered to reflect a germ cell profile and the expression decreases during the initial primordial germ cell stage [19,27].