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61.
急性髓细胞白血病(AML)是一组在发病机制和临床行为方面差异较大的疾病.在急性早幼粒细胞白血病中(APL),PML-RARα是APL的关键驱动(driver)突变,具有显性负的调控作用,影响髓系分化、凋亡和DNA复制和修复,其特殊结构使其成为全反式维甲酸和三氧化二砷的靶标.随着第二代测序技术的发展,在AML中发现了一些新的基因突变,其中DNA甲基转移酶3A(DNMT3A)突变是与表观遗传学相关的、与AML较差预后有关的基因事件.在1185例AML的基因分析中,研究发现与表观遗传学相关的第Ⅲ类突变与老年、高WBC及较差的临床预后有关.AML的发病是多步骤的,涉及不同通路上不同分子事件的相互作用,目前认为影响转录因子和信号传导通路的分子事件相互作用是AML完全发病的重要模式之一. 相似文献
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A. Pérez‐Figueroa 《Molecular ecology resources》2013,13(3):522-527
In this study msap, an R package which analyses methylation‐sensitive amplified polymorphism (MSAP or MS‐AFLP) data is presented. The program provides a deep analysis of epigenetic variation starting from a binary data matrix indicating the banding pattern between the isoesquizomeric endonucleases HpaII and MspI, with differential sensitivity to cytosine methylation. After comparing the restriction fragments, the program determines if each fragment is susceptible to methylation (representative of epigenetic variation) or if there is no evidence of methylation (representative of genetic variation). The package provides, in a user‐friendly command line interface, a pipeline of different analyses of the variation (genetic and epigenetic) among user‐defined groups of samples, as well as the classification of the methylation occurrences in those groups. Statistical testing provides support to the analyses. A comprehensive report of the analyses and several useful plots could help researchers to assess the epigenetic and genetic variation in their MSAP experiments. msap is downloadable from CRAN ( http://cran.r-project.org/ ) and its own webpage ( http://msap.r-forge.R-project.org/ ). The package is intended to be easy to use even for those people unfamiliar with the R command line environment. Advanced users may take advantage of the available source code to adapt msap to more complex analyses. 相似文献
64.
M. J. A. M. Clausen L. J. Melchers M. F. Mastik L. Slagter-Menkema H. J. M. Groen B. F. A. M. van der Laan 《Epigenetics》2016,11(9):653-663
Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC. 相似文献
65.
Jean-Jacques Candelier 《Cell Adhesion & Migration》2016,10(1-2):226-235
ABSTRACTThe hydatidiform mole (HM) is a placental pathology of androgenetic origin. Placental villi have an abnormal hyperproliferation event and hydropic degeneration. Three situations can be envisaged at its origin: 1. The destruction/expulsion of the female pronucleus at the time of fertilization by 1 or 2 spermatozoa with the former being followed by an endoreplication of the male pronucleus leading to a complete hydatidiform mole (CHM) 2. A triploid zygote (fertilization by 2 spermatozoa) leading to a partial hydatidiform mole (PHM) but can also lead to haploid and diploid clones. The diploid clone may produce a normal fetus while the haploid clone after endoreplication generates a CHM 3. A nutritional defect during the differentiation of the oocytes or the deterioration of the limited oxygen pressure during the first trimester of gestation may lead to the formation of a HM.In countries with poor medical health care system, moles (mainly the CHM) can become invasive or, in rare cases, lead to gestational choriocarcinomas. 相似文献
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Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy 下载免费PDF全文
Jiaxin Yang Menghui Li Zhenyu Zhang Keng Shen 《Journal of cellular and molecular medicine》2016,20(4):581-593
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular‐targeted therapy. Poly (ADP‐ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)‐related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival. 相似文献
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Sofia J. van Moorsel Marc W. Schmid Niels C. A. M. Wagemaker Thomas van Gurp Bernhard Schmid Philippine Vergeer 《Molecular ecology》2019,28(17):4097-4117
In long‐term grassland experiments, positive biodiversity effects on plant productivity commonly increase with time. Subsequent glasshouse experiments showed that these strengthened positive biodiversity effects persist not only in the local environment but also when plants are transferred into a common environment. Thus, we hypothesized that community diversity had acted as a selective agent, resulting in the emergence of plant monoculture and mixture types with differing genetic composition. To test our hypothesis, we grew offspring from plants that were grown for eleven years in monoculture or mixture environments in a biodiversity experiment (Jena Experiment) under controlled glasshouse conditions in monocultures or two‐species mixtures. We used epiGBS, a genotyping‐by‐sequencing approach combined with bisulphite conversion, to provide integrative genetic and epigenetic (i.e., DNA methylation) data. We observed significant divergence in genetic and DNA methylation data according to selection history in three out of five perennial grassland species, namely Galium mollugo, Prunella vulgaris and Veronica chamaedrys, with DNA methylation differences mostly reflecting the genetic differences. In addition, current diversity levels in the glasshouse had weak effects on epigenetic variation. However, given the limited genome coverage of the reference‐free bisulphite method epiGBS, it remains unclear how much of the differences in DNA methylation was independent of underlying genetic differences. Our results thus suggest that selection of genetic variants, and possibly epigenetic variants, caused the rapid emergence of monoculture and mixture types within plant species in the Jena Experiment. 相似文献
70.
Heena Dhiman Matthias P. Gerstl David Ruckerbauer Michael Hanscho Heinz Himmelbauer Colin Clarke Niall Barron Jürgen Zanghellini Nicole Borth 《Biotechnology journal》2019,14(7)
The increasingdemandfor biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity, and product quality. As these depend on energy generation, here the genomic variation in nuclear genes associated with mitochondria and energy metabolism and the mitochondrial genome of 14 cell lines is investigated. The variants called enable reliable tracing of lineages. Unique sequence variations are observed in cell lines adapted to grow in protein‐free media, enriched in signaling pathways or mitogen‐activated protein kinase 3. High‐producing cell lines bear unique mutations in nicotinamide adenine dinucleotide (NADH) dehydrogenase (ND2 and ND4) and in peroxisomal acyl‐CoA synthetase (ACSL4), involved in lipid metabolism. As phenotypes are determined not only by functional mutations, but also by the exquisite regulation of expression patterns, it is not surprising that ≈50% of the genes investigated here are found to be differentially methylated and thus epigenetically controlled, enabling a clear distinction of high producers, and cells adapted to a minimal, glutamine (Gln)‐free medium. Similar pathways are enriched as those identified by genome variation. This strengthens the hypothesis that these phenomena act together to define cell behavior. 相似文献