The evolution of pleomorphic xanthoastrocytoma: from genesis to molecular alterations and mimics

2022 ◽  
Author(s):  
Swati Mahajan ◽  
Iman Dandapath ◽  
Ajay Garg ◽  
Mehar C. Sharma ◽  
Vaishali Suri ◽  
...  
Keyword(s):  
Pleomorphic Xanthoastrocytoma ◽  
Molecular Alterations

scholarly journals Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas

2020 ◽  
Vol 22 (10) ◽  
pp. 1474-1483 ◽  
Author(s):  
Kohei Fukuoka ◽  
Yasin Mamatjan ◽  
Ruth Tatevossian ◽  
Michal Zapotocky ◽  
Scott Ryall ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Infiltration ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Additional Information ◽  
Molecular Alterations

Abstract Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers. Results Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014). Conclusion The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.

scholarly journals Acquired ATRX Loss and ALT Phenotype Through Tumor Recurrences in a Case of Pleomorphic Xanthoastrocytoma Suggest Their Possible Roles in Tumor Progression

2020 ◽  
Vol 79 (9) ◽  
pp. 1011-1014
Author(s):  
Pierre Dal Col ◽  
Delphine Poncet ◽  
Romain Rivoirard ◽  
François Vassal ◽  
Emilie Bernichon ◽  
...  
Keyword(s):  
Young Adults ◽  
Tumor Progression ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Tumor Evolution ◽  
Molecular Alterations ◽  
Astrocytic Glioma ◽  
Alternative Lengthening ◽  
Cdkn2a Deletion

Abstract Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in children or young adults. Molecular alterations in PXA are not fully known, especially those associated with tumor progression. We describe a patient with several relapses of a PXA. The tumor showed an acquired ATRX loss through tumor evolution. We tested alternative lengthening of telomeres (ALT) with the C-circle test. While the test was negative in the first tumor, a high circle activity was detected in the last relapse, suggesting an acquired ALT phenotype. Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

2020 ◽  
Vol 27 (8) ◽  
pp. 1367-1381 ◽  
Author(s):  
Sarah Visentin ◽  
Mirela Sedić ◽  
Sandra Kraljević Pavelić ◽  
Krešimir Pavelić
Keyword(s):  
Cancer Progression ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Metastatic Progression ◽  
Therapeutic Concept ◽  
Molecular Alterations ◽  
Tumour Metastasis ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

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