Gene expression profiles of complete hydatidiform moles and XBP1-overexpressing cell lines associated with progression to gestational trophoblastic tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252907 | GEO | 2024/12/22
REPOSITORIES: GEO
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Project description:The trophoblastic disease is a general term for diseases that cause abnormal growth of trophoblasts, the most frequent form of which is called hydatidiform mole (CHM). CHM cell lines (Hmol1-3B and Hmol1-2C) were established in our laboratory (Yamamoto E, et al. Int J Mol Med. 2017 Sep; 40(3): 614–622). In this study, XBP1 was overexpressed, and RNA sequencing was performed to investigate the role of XBP1 in CHM.
2024-12-21 | GSE252905 | GEO
Project description:ObjectivePathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.Material and methodsThree unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes.ResultsNLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.ConclusionsWe found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.
| S-EPMC10230829 | biostudies-literature
Project description: Not available
| S-EPMC6483742 | biostudies-literature
Project description:BackgroundHydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear.ObjectivesTo systematically review the evidence for the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy.Search methodsWe performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and EMBASE (1980 to week 9, 2012). The search strategy was developed using free text and medical subject headings (MESH). We handsearched reference lists of relevant literature to identify additional studies.Selection criteriaWe included randomised controlled trials (RCTs) of P-Chem for HM.Data collection and analysisTwo review authors independently assessed studies for inclusion in the review and extracted data using a specifically designed data collection form. Meta-analyses were performed by pooling data from individual trials using RevMan 5.1 software.Main resultsWe included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality.P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; RR 0.37; 95% confidence interval (CI) 0.24 to 0.57; I(2) = 0%; P < 0.00001), However, owing to the poor quality of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28; 95% CI 0.10 to 0.73; P = 0.01), therefore we consider this evidence to be of a low quality.The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72; 95% CI 13.19 to 44.24; P = 0.0003) and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10; 95% CI 0.52 to 1.68; P = 0.0002). We consider this evidence to be of a low to very low quality for similar reasons to those listed above.There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes.Authors' conclusionsP-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delay treatment of GTN and expose women unnecessarily to toxic side effects, this practice cannot currently be recommended.
| S-EPMC6457751 | biostudies-literature
Project description:Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10-6), and immune genes (OR = 1.82, p = 7.34 × 10-18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.
| S-EPMC6829352 | biostudies-literature
Project description:Transcriptome analysis for XBP1 overexpressing complete hydatidiform mole-derived cell lines
| PRJNA1063209 | ENA
Project description:The haplotype map constructed by the International HapMap Project is a valuable source for the studies of disease genes, population structure, and evolution. In the Project, haplotypes have been inferred from experimentally determined genotypes, and are fairly accurate for Caucasians and Africans since the inference was based on the genotypes of trios. However, the inference for the Asians populations was less accurate, because of the lack of familial information. Here we assessed how the error in the inference can affect downstream studies, especially the analysis of recent positive selections, by comparing the results of the analyses using the data of HapMap JPT and of definitive haplotypes (DHaplo-DB) determined by us from a collection of Japanese complete hydatidiform moles (CHM), each of which carries a genome derived from a single sperm. We found that the error in JPT was not uniform throughout the genome, and the statistics for recent positive selection was significantly affected. Keywords: Definitive haplotype determination using CHMs, which carry haploid genomes. 100 CHM samples collected throughout Japan were analyzed by Affymetrix Genechip Mapping 500K Set array.
2010-04-05 | E-GEOD-12713 | biostudies-arrayexpress
Project description:The haplotype map constructed by the International HapMap Project is a valuable source for the studies of disease genes, population structure, and evolution. In the Project, haplotypes have been inferred from experimentally determined genotypes, and are fairly accurate for Caucasians and Africans since the inference was based on the genotypes of trios. However, the inference for the Asians populations was less accurate, because of the lack of familial information. Here we assessed how the error in the inference can affect downstream studies, especially the analysis of recent positive selections, by comparing the results of the analyses using the data of HapMap JPT and of definitive haplotypes (DHaplo-DB) determined by us from a collection of Japanese complete hydatidiform moles (CHM), each of which carries a genome derived from a single sperm. We found that the error in JPT was not uniform throughout the genome, and the statistics for recent positive selection was significantly affected. Keywords: Definitive haplotype determination using CHMs, which carry haploid genomes.
2009-05-12 | GSE12713 | GEO
Project description:We analyzed high-dimensional RNA data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Of the 14,022 protein-coding genes expressed in all samples, 3729 were differentially expressed (DE) in CHMs of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001) of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10−6), and immune genes (OR = 1.82, p = 7.34 × 10−18), of which 73% were up-regulated. DNA methylation enzymes and histone demethylases were dysregulated. “Cytokine–cytokine receptor interaction” was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways.
2019-10-31 | GSE138250 | GEO
Project description:Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1-/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.
| S-EPMC6218808 | biostudies-literature