Molecular Diagnostics of Gliomas

2011 ◽  
Vol 135 (5) ◽  
pp. 558-568 ◽  
Author(s):  
Marina N. Nikiforova ◽  
Ronald L. Hamilton
Keyword(s):  
Molecular Markers ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Diagnostic Value ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Molecular Diagnostic Techniques ◽  
Isocitrate Dehydrogenase 1 ◽  
Detection Techniques ◽  
Anaplastic Gliomas

Abstract Context.—Gliomas are the most common primary brain tumors of adults and include a variety of histologic types and morphologies. Histologic evaluation remains the gold standard for glioma diagnosis; however, diagnostic difficulty may arise from tumor heterogeneity, overlapping morphologic features, and tumor sampling. Recently, our knowledge about the genetics of these tumors has expanded, and new molecular markers have been developed. Some of these markers have shown diagnostic value, whereas others are useful prognosticators for patient survival and therapeutic response. Objective.—To review the most clinically useful molecular markers and their detection techniques in gliomas. Data Sources.—Review of the pertinent literature and personal experience with the molecular testing in gliomas. Conclusions.—This article provides an overview of the most common molecular markers in neurooncology, including 1p/19q codeletion in oligodendroglial tumors, mutations in the isocitrate dehydrogenase 1 and 2 genes in diffuse gliomas, hypermethylation of the O6-methylguanine-DNA methyltransferase gene promoter in glioblastomas and anaplastic gliomas, alterations in the epidermal growth factor receptor and phosphatase and tensin homolog genes in high-grade gliomas, as well as BRAF alterations in pilocytic astrocytomas. Molecular testing of gliomas is increasingly used in routine clinical practice and requires that neuropathologists be familiar with these genetic markers and the molecular diagnostic techniques for their detection.

scholarly journals A practical review of prognostic correlations of molecular biomarkers in glioblastoma

2015 ◽  
Vol 38 (3) ◽  
pp. E4 ◽  
Author(s):  
Michael Karsy ◽  
Jayson A. Neil ◽  
Jian Guan ◽  
Mark A. Mahan ◽  
Howard Colman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Markers ◽  
Growth Factor ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Predictive Biomarker ◽  
Isocitrate Dehydrogenase 1 ◽  
Tensin Homolog ◽  
Formidable Challenge ◽  
Phosphoinositide 3 Kinase

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylgua-nine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), Phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

scholarly journals Correlation Between Tumor Molecular Markers and Perioperative Epilepsy in Patients With Glioma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Song ◽  
Xingyun Quan ◽  
Chaoyi Chen ◽  
Ligang Chen ◽  
Jie Zhou
Keyword(s):  
Molecular Markers ◽  
Dna Methyltransferase ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Growth Factor Receptor ◽  
Idh1 Mutation ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Isocitrate Dehydrogenase 1 ◽  
The Relationship

Purpose: Tumors derived from the neuroepithelium are collectively termed gliomas and are the most common malignant primary brain tumor. Epilepsy is a common clinical symptom in patients with glioma, which can impair neurocognitive function and quality of life. Currently, the pathogenesis of glioma-related epilepsy is not fully described. Therefore, it is necessary to further understand the mechanism of seizures in patients with glioma. In this study, a comprehensive meta-analysis was conducted to investigate the relationship between five commonly used tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma.Methods: PubMed, EMBASE, and Cochrane Library databases were searched for related research studies. Odds ratio and the corresponding 95% confidence interval were used as the main indicators to evaluate the correlation between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma.Results: A total of 12 studies were included in this meta-analysis. The results showed that isocitrate dehydrogenase 1 (IDH1) mutation was significantly correlated with the incidence of perioperative epilepsy. A subgroup analysis showed that IDH1 was significantly correlated with the incidence of preoperative epilepsy, but not with intraoperative and postoperative epilepsy. There was no correlation between O6-methylguanine-DNA methyltransferase methylation and 1p/19q deletion and the incidence of perioperative epilepsy. Tumor protein p53 and epidermal growth factor receptor could not be analyzed because of the limited availability of relevant literature. There was no significant heterogeneity or publication bias observed among the included studies.Conclusion: The present meta-analysis confirms the relationship between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma. The present results provide more comprehensive evidence for the study of the pathogenesis of glioma-related epilepsy. Our research may offer a new method for the treatment of perioperative seizures in patients with glioma.

scholarly journals Intratumoral Susceptibility Signals Reflect Biomarker Status in Gliomas

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ling-Wei Kong ◽  
Jin Chen ◽  
Heng Zhao ◽  
Kun Yao ◽  
Sheng-Yu Fang ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Dna Methyltransferase ◽  
Area Under The Curve ◽  
Predictive Ability ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Methylguanine Dna Methyltransferase ◽  
Non Invasive ◽  
Marker Status ◽  
The Relationship

AbstractSusceptibility-weighted imaging (SWI) can be a useful tool to depict vascular structures in brain tumors as well as micro-bleedings, which represent tumor invasion to blood vessels and could also be representative of tumoral angiogenesis. In this study, we investigated the relationship between SWI features and glioma grades, and the expression of key molecular markers isocitrate dehydrogenase 1 (IDH1), O-6-methylguanine-DNA methyltransferase (MGMT), and 1p19q. The gliomas were graded according to the intratumoral susceptibility signals (ITSS). We used the Mann-Whitney test to analyze the relationship between ITSS grades and the pathological level and status of these markers. Additionally, the area under the curve (AUC) was used to determine the predictive value of glioma SWI characteristics for the molecular marker status. In these cases, the ITSS grades of low-grade gliomas (LGG) were significantly lower than those of high-grade gliomas (HGG). Similarly, the ITSS grades of gliomas with IDH1 mutations and MGMT methylation were significantly lower than those of gliomas with Wild-type IDH1 and unmethylated MGMT. However, ITSS grades showed no relationship with 1p19q deletion status, while they did show significant predictive ability for glioma grade, IDH1 mutation, and MGMT methylation. These findings indicate an association between some molecular markers and cerebral microbleeds in gliomas, providing a new avenue for non-invasive prediction of molecular genetics in gliomas and an important basis for preoperative personalized surgical treatment based on molecular pathology.

scholarly journals Molecular Classification of Diffuse Gliomas

2020 ◽  
Vol 47 (4) ◽  
pp. 464-473
Author(s):  
Navya Kalidindi ◽  
Rosemarylin Or ◽  
Sam Babak ◽  
Warren Mason
Keyword(s):  
Dna Methylation ◽  
Molecular Markers ◽  
World Health ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Gliomas ◽  
Diffuse Gliomas ◽  
The Impact

ABSTRACT:Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

scholarly journals Leishmania tarentolae and Leishmania infantum in humans, dogs and cats in the Pelagie archipelago, southern Italy

2021 ◽  
Vol 15 (9) ◽  
pp. e0009817
Author(s):  
Roberta Iatta ◽  
Jairo Alfonso Mendoza-Roldan ◽  
Maria Stefania Latrofa ◽  
Antonio Cascio ◽  
Emanuele Brianti ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Molecular Diagnostic ◽  
Enzyme Linked Immunosorbent Assay ◽  
Molecular Testing ◽  
Molecular Diagnostic Techniques ◽  
Serum Samples ◽  
Serological Tests ◽  
Leishmania Tarentolae ◽  
Human Samples ◽  
Animal Populations

Visceral leishmaniasis (VL) caused by Leishmania infantum is endemic in the Mediterranean basin with most of the infected human patients remaining asymptomatic. Recently, the saurian-associated Leishmania tarentolae was detected in human blood donors and in sheltered dogs. The circulation of L. infantum and L. tarentolae was investigated in humans, dogs and cats living in the Pelagie islands (Sicily, Italy) by multiple serological and molecular testing. Human serum samples (n = 346) were tested to assess the exposure to L. infantum by immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) and to L. tarentolae by IFAT. Meanwhile, sera from dogs (n = 149) and cats (n = 32) were tested for both Leishmania species by IFAT and all blood samples by specific sets of real time-PCR for L. infantum and L. tarentolae. The agreement between serological tests performed for human samples, and between serological and molecular diagnostic techniques for both human and animal samples were also assessed. Overall, 41 human samples (11.8%, 95% CI: 8.9–15.7) were positive to L. infantum (5.2%, 95% CI: 3.3–8.1), L. tarentolae (5.2%, 95% CI: 3.3–8.1) and to both species (1.4%, 95% CI: 0.6–3.3) by serology and/or molecular tests. A good agreement among the serological tests was determined. Both Leishmania spp. were serologically and/or molecularly detected in 39.6% dogs and 43.7% cats. In addition to L. infantum, also L. tarentolae circulates in human and animal populations, raising relevant public health implications. Further studies should investigate the potential beneficial effects of L. tarentolae in the protection against L. infantum infection.

Advances in Treatment of Lung Cancer With Targeted Therapy

2012 ◽  
Vol 136 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Philip T. Cagle ◽  
Lucian R. Chirieac
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Diagnostic Techniques ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Molecular Diagnostic Techniques ◽  
Molecular Abnormalities ◽  
Pathologic Features

Context.—Ongoing preclinical investigations and clinical trials involving new targeted therapies promise to improve survival for patients with lung cancer. Targeted therapeutic agents, based on genetic mutations and signaling pathways altered in lung cancer, have added significantly to our armamentarium for lung cancer treatment while minimizing drug toxicity. To date, 4 targeted therapies have been approved for treatment of lung cancer by the US Food and Drug Administration: gefitinib in 2002, erlotinib in 2003, bevacizumab in 2006, and crizotinib in 2011. Objective.—To review targeted therapies in lung cancer, the molecular biomarkers that identify patients likely to benefit from these targeted therapies, the basic molecular biology principles, selected molecular diagnostic techniques, and pathologic features correlated with molecular abnormalities in lung cancer. To review new molecular abnormalities described in lung cancer that are predictive for response to novel promising targeted agents in various phases of clinical trials. Data Sources.—Review of the literature covering the molecular abnormalities of lung cancer with a focus on the molecular diagnostics and targeted therapy. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of lung cancer. Conclusions.—Molecular testing of lung cancer expands the expertise of the pathologist, who will identify the tumor markers that are predictive of sensitivity or resistance to various targeted therapies and allow patients with cancer to be selected for highly effective and less toxic therapies.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Molecular and Circulating Biomarkers of Brain Tumors

2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Methylguanine Dna Methyltransferase ◽  
The Central Nervous System

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations.While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.

scholarly journals Moraxella catarrhalis: from Emerging to Established Pathogen

2002 ◽  
Vol 15 (1) ◽  
pp. 125-144 ◽  
Author(s):  
Cees M. Verduin ◽  
Cees Hol ◽  
André Fleer ◽  
Hans van Dijk ◽  
Alex van Belkum
Keyword(s):  
Moraxella Catarrhalis ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Diagnostic Techniques ◽  
Human Infection ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Pathogenic Potential ◽  
The Past

SUMMARY Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of Β-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

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