scholarly journals A case of intraplacental gestational choriocarcinoma; characterised by the methylation pattern of the early placenta and an absence of driver mutations

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Philip Savage ◽  
David Monk ◽  
Jose R. Hernandez Mora ◽  
Nick van der Westhuizen ◽  
Jennifer Rauw ◽  
...  
Keyword(s):  
Methylation Pattern ◽  
Driver Mutations ◽  
Gestational Choriocarcinoma ◽  
Early Placenta

scholarly journals Distinct genomic profiles of gestational choriocarcinoma, a unique cancer of pregnant tissues

2020 ◽  
Vol 52 (12) ◽  
pp. 2046-2054
Author(s):  
Seung-Hyun Jung ◽  
Youn Jin Choi ◽  
Min Sung Kim ◽  
Hyeon-Chun Park ◽  
Mi-Ryung Han ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Neutral Loss ◽  
Hydatidiform Mole ◽  
Driver Mutations ◽  
Cancer Genes ◽  
Single Nucleotide ◽  
Gestational Choriocarcinoma ◽  
Whole Exome ◽  
Late Event ◽  
Invasive Mole

AbstractLittle is known about genomic alterations of gestational choriocarcinoma (GC), unique cancer that originates in pregnant tissues, and the progression mechanisms from the nonmalignant complete hydatidiform mole (CHM) to GC. Whole-exome sequencing (20 GCs) and/or single-nucleotide polymorphism microarray (29 GCs) were performed. We analyzed copy-neutral loss-of-heterozygosity (CN-LOH) in 29 GCs that exhibited androgenetic CN-LOHs (20 monospermic, 8 dispermic) and no CN-LOH (one with NLRP7 mutation). Most GCs (25/29) harboring recurrent copy number alterations (CNAs) and gains on 1q21.1-q44 were significantly associated with poor prognosis. We detected five driver mutations in the GCs, most of which were chromatin remodeling gene (ARID1A, SMARCD1, and EP300) mutations but not in common cancer genes such as TP53 and KRAS. One patient’s serial CHM/invasive mole/GC showed consistent CN-LOHs, but only the GC harbored CNAs, indicating that CN-LOH is an early pivotal event in HM-IM-GC development, and CNAs may be a late event that promotes CHM progression to GC. Our data indicate that GCs have unique profiles of CN-LOHs, mutations and CNAs that together differentiate GCs from non-GCs. Practically, CN-LOH and CNA profiles are useful for the molecular diagnosis of GC and the selection of GC patients with poor prognosis for more intensive treatments, respectively.

scholarly journals Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma

2019 ◽  
Vol 476 (1) ◽  
pp. 135-146 ◽  
Author(s):  
Sanne Venneker ◽  
Karoly Szuhai ◽  
Pancras C. W. Hogendoorn ◽  
Judith V. M. G. Bovée
Keyword(s):  
Giant Cell ◽  
Giant Cell Tumour ◽  
Point Mutations ◽  
Methylation Pattern ◽  
Cell Tumour ◽  
Driver Mutations ◽  
Diagnostic Tools ◽  
Epigenetic Alterations ◽  
Dna Hypermethylation ◽  
Specific Point

AbstractRecently, specific driver mutations were identified in chondroblastoma, giant cell tumour of bone and central cartilaginous tumours (specifically enchondroma and central chondrosarcoma), sharing the ability to induce genome-wide epigenetic alterations. In chondroblastoma and giant cell tumour of bone, the neoplastic mononuclear stromal-like cells frequently harbour specific point mutations in the genes encoding for histone H3.3 (H3F3A and H3F3B). The identification of these driver mutations has led to development of novel diagnostic tools to distinguish between chondroblastoma, giant cell tumour of bone and other giant cell containing tumours. From a biological perspective, these mutations induce several global and local alterations of the histone modification marks. Similar observations are made for central cartilaginous tumours, which frequently harbour specific point mutations in the metabolic enzymes IDH1 or IDH2. Besides an altered methylation pattern on histones, IDH mutations also induce a global DNA hypermethylation phenotype. In all of these tumour types, the mutation-driven epigenetic alterations lead to a highly altered transcriptome, resulting for instance in alterations in differentiation. These genomic alterations have diagnostic impact. Further research is needed to identify the genes and signalling pathways that are affected by the epigenetic alterations, which will hopefully lead to a better understanding of the biological mechanism underlying tumourigenesis.

scholarly journals Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward Improved Personalized Prognostication

2018 ◽  
Vol 103 (12) ◽  
pp. 4511-4523 ◽  
Author(s):  
Juliane Lippert ◽  
Silke Appenzeller ◽  
Raimunde Liang ◽  
Silviu Sbiera ◽  
Stefan Kircher ◽  
...  
Keyword(s):  
Drug Targets ◽  
Characteristic Curve ◽  
Point Mutations ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Methylation Pattern ◽  
Molecular Signature ◽  
Driver Mutations ◽  
Repair System ◽  
Ki 67

Abstract Context Adrenocortical carcinoma (ACC) has a heterogeneous prognosis, and current medical therapies have limited efficacy in its advanced stages. Genome-wide multiomics studies identified molecular patterns associated with clinical outcome. Objective Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine. Design In total, 117 tumor samples from 107 patients with ACC were analyzed. Targeted next-generation sequencing of 160 genes and pyrosequencing of 4 genes were applied to formalin-fixed, paraffin-embedded (FFPE) specimens to detect point mutations, copy number alterations, and promoter region methylation. Molecular results were combined with clinical/histopathological parameters (tumor stage, age, symptoms, resection status, and Ki-67) to predict progression-free survival (PFS). Results In addition to known driver mutations, we detected recurrent alterations in genes not previously associated with ACC (e.g., NOTCH1, CIC, KDM6A, BRCA1, BRCA2). Best prediction of PFS was obtained integrating molecular results (more than one somatic mutation, alterations in Wnt/β-catenin and p53 pathways, high methylation pattern) and clinical/histopathological parameters into a combined score (P < 0.0001, χ2 = 68.6). Accuracy of prediction for early disease progress was 83.3% (area under the receiver operating characteristic curve: 0.872, 95% confidence interval 0.80 to 0.94). Furthermore, 17 potentially targetable alterations were found in 64 patients (e.g., in CDK4, NOTCH1, NF1, MDM2, and EGFR and in DNA repair system). Conclusions This study demonstrates that molecular profiling of FFPE tumor samples improves prognostication of ACC beyond clinical/histopathological parameters and identifies new potential drug targets. These findings pave the way to precision medicine in this rare disease.

Ultrastructure of Choriocarcinoma in Vitro

1969 ◽  
Vol 27 ◽  
pp. 362-363
Author(s):  
John C. Garancis ◽  
R. A. Pattillo
Keyword(s):  
Cell Line ◽  
Physiological Function ◽  
Cell System ◽  
Bewo Cell ◽  
Bewo Cells ◽  
Gestational Choriocarcinoma ◽  
Bewo Cell Line

Growth of cell system (BeWo-cell line) derived from human gestational choriocarcinoma has been established and continuously maintained in-vitro. Furthermore, it is evident from the previous studies that this cell line has retained the physiological function of the placental trophoblasts, namely the synthesis of human chorionic gonadotrophil(HCG).The BeWo cells were relatively small and possessed single nuclei, thus indicating that this cell line consists exclusively of cytotrophoblasts. In some instances cells appeared widely separated and their lateral surfaces were provided with numerous microvilli (Fig.1).

Comparison of Choriocarcinoma and Normal Placenta

1971 ◽  
Vol 29 ◽  
pp. 324-325
Author(s):  
John C. Garancis ◽  
Roland A. Pattillo ◽  
Robert O. Hussa ◽  
Jon V. Straumfjord
Keyword(s):  
Cell Lines ◽  
Small Cells ◽  
Tissue Cultures ◽  
Glycogen Depletion ◽  
Cell Surfaces ◽  
Intercellular Spaces ◽  
Concomitant Increase ◽  
Gestational Choriocarcinoma ◽  
Cytoplasmic Glycogen ◽  
Normal Placenta

Two different cell lines (Be-Wo and Jar) of human gestational choriocarcinoma have been maintained in continuous tissue culture for a period of four and two years respectively without losing the ability to elaborate human chorionic gonadotropin (HCG). Tissue cultures, as revealed by electron microscopy, consisted of small cells with single nuclei. In some instances cell surfaces were provided with microvilli but more often the intercellular spaces were narrow and bridged by desmosomes. However, syncytium was not formed. Endoplasmic reticulum (ER) was poorly developed in both cell lines, except in some Be-Wo cells it was prominent. Golgi complex, lysosomes and numerous free ribosomes, as well as excessive cytoplasmic glycogen, were present in all cells (Fig. 1). Glycogen depletion and concomitant increase of ER were observed in many cells following a single dose of 10 ugm/ml of adrenalin added to medium (Fig. 2).

Novel driver mutations in thyroid cancer recurrence

2017 ◽  
Author(s):  
Hannah Nieto ◽  
Alice Fletcher ◽  
Rebecca Thompson ◽  
Kate Baker ◽  
Mohammed Alshahrani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Recurrence ◽  
Driver Mutations ◽  
Thyroid Cancer Recurrence

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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