Publications by authors named "Henning Boldt"

IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas.

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Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation.

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Article Synopsis
  • Aggressive pituitary neuroendocrine tumors (PitNETs) often grow despite treatment and can metastasize, making them particularly challenging to manage.
  • This study analyzed tumor samples from 64 patients to investigate genetic markers, finding distinct patterns between aggressive/metastatic tumors and benign ones through genome-wide methylation and chromosomal analyses.
  • The results indicate potential biomarkers that could help in identifying high-risk patients earlier, refining treatment protocols, and improving outcomes for those with aggressive pituitary tumors.
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  • The study investigates whether DNA methylation profiling can serve as a prognostic marker to predict regrowth potential in pituitary adenomas after surgery.
  • It involved analyzing 42 pituitary macroadenoma samples using Illumina's MethylationEPIC array, leading to the identification of distinct DNA methylation clusters among tumors.
  • Although the results showed no statistically significant differences in regrowth rates between clusters, there were indications that certain methylation patterns might correlate with higher regrowth tendencies.
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Background: There are no generally accepted criteria for selecting patients with recurrent glioblastoma for surgery. This retrospective study in a Danish population-based cohort aimed to identify prognostic factors affecting postoperative survival after repeated surgery for recurrent glioblastoma and to test if the preoperative New Scale for Recurrent Glioblastoma Surgery (NSGS) developed by Park CK et al could assist in the selection of patients for repeat glioblastoma surgery.

Methods: Clinical data from 66 patients with recurrent glioblastoma and repeated surgery were analyzed.

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Article Synopsis
  • MEN1 is a rare genetic syndrome caused by mutations in the menin 1 gene, leading to tumors in multiple endocrine glands, particularly affecting parathyroid, pancreatic, and pituitary glands.
  • Primary hyperparathyroidism is the most common manifestation, followed by pancreatic neuroendocrine tumors, and recent studies have identified ependymoma as another potential neoplasm associated with MEN1.
  • The text introduces a new tumor subtype linked to MEN1 called Pleomorphic Xanthoastocytoma grade 3 differential pathology (PDP), suggesting that it may arise from specific genetic variants related to the MEN1 gene and associated factors.
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer with an overall 5-year survival of around 10 %. New prognostic tools to stratify patients are needed. Our main aim was to evaluate the prognostic value of overall copy number variation (CNV) burden in surgically treated PDAC.

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Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types.

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Background: Paraganglioma occurs rarely in the sellar/parasellar region. Here, we report a patient with malignant paraganglioma with primary sellar location with unusual genetic and imaging features.

Case Presentation: A 31-year-old male presented with mild hypertension, headache, nausea, and vomiting.

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Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma.

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Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology.

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: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence.

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Glioblastoma multiforme is the most common primary brain tumor and among the most lethal types of cancer. Several mono-target small molecule-inhibitors have been investigated as novel therapeutics, thus far with poor success. In this study we investigated the anticancer effects of SB747651A, a multi-target small-molecule inhibitor, in three well characterized patient-derived glioblastoma spheroid cultures and a murine orthotopic xenograft model.

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Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs.

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Most glioblastoma patients have a dismal prognosis, although some survive several years. However, only few biomarkers are available to predict the disease course. EGR1 and EGR3 have been linked to glioblastoma stemness and tumour progression, and this study aimed to investigate their spatial expression and prognostic value in gliomas.

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Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains.

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Rosette-forming glioneuronal tumor (RGNT) is a rare brain neoplasm that primarily affects young adults. Although alterations affecting the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathway have been associated with this low-grade entity, comprehensive molecular investigations of RGNT in larger series have not been performed to date, and an integrated view of their genetic and epigenetic profiles is still lacking. Here we describe a genome-wide DNA methylation and targeted sequencing-based characterization of a molecularly distinct class of tumors (n = 30), initially identified through genome-wide DNA methylation screening among a cohort of > 30,000 tumors, of which most were diagnosed histologically as RGNT.

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The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes temozolomide-induced alkylation, thereby preventing DNA damage and cytotoxicity. We investigated the prognostic effect of different MGMT methylation levels on overall and progression-free survival in 327 patients with primary glioblastoma undergoing standard treatment. We obtained MGMT methylation level in 4 CpG sites using pyrosequencing.

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Diagnostics of tumours of the central nervous system has for decades been based entirely on microscopy. A con-siderable degree of diagnostic interobserver variability has been observed due to imprecise histological criteria. In the revised WHO classification for central nervous system tumours from 2016, several diagnoses are now defined by both histological and molecular features and constitute "integrated diagnoses".

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Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown.

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Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas.

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Aquaporin-4 (AQP4) is the predominant water channel in the brain and is expressed in high density in astrocytes. By fluxing water along osmotic gradients, AQP4 contributes to brain volume and ion homeostasis. Here we ask whether deletion of Aqp4 leads to upregulation of the gap junctional proteins connexin-43 (Cx43) and connexin-30 (Cx30).

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Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery.

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