We are analyzing https://link.springer.com/article/10.1186/s40478-015-0265-4.

Title:
PI3 kinase mutations and mutational load as poor prognostic markers in diffuse glioma patients | Acta Neuropathologica Communications
Description:
Introduction Recent advances in molecular diagnostics allow diffuse gliomas to be classified based on their genetic changes into distinct prognostic subtypes. However, a systematic analysis of all molecular markers has thus far not been performed; most classification schemes use a predefined and select set of genes/molecular markers. Here, we have analysed the TCGA dataset (combined glioblastoma (GBM) and lower grade glioma (LGG) datasets) to identify all prognostic genetic markers in diffuse gliomas in order to generate a comprehensive classification scheme. Results Of the molecular markers investigated (all genes mutated at a population frequency >1.7 % and frequent chromosomal imbalances) in the entire glioma dataset, 57 were significantly associated with overall survival. Of these, IDH1 or IDH2 mutations are associated with lowest hazard ratio, which confirms IDH as the most important prognostic marker in diffuse gliomas. Subsequent subgroup analysis largely confirms many of the currently used molecular classification schemes for diffuse gliomas (ATRX or TP53 mutations, 1p19q codeletion). Our analysis also identified PI3-kinase mutations as markers of poor prognosis in IDH-mutated + ATRX/TP53 mutated diffuse gliomas, median survival 3.7 v. 6.3 years (P = 0.02, Hazard rate (HR) 2.93, 95 % confidence interval (CI) 1.16 – 7.38). PI3-kinase mutations were also prognostic in two independent datasets. In our analysis, no additional molecular markers were identified that further refine the molecular classification of diffuse gliomas. Interestingly, these molecular classifiers do not fully explain the variability in survival observed for diffuse glioma patients. We demonstrate that tumor grade remains an important prognostic factor for overall survival in diffuse gliomas, even within molecular glioma subtypes. Tumor grade was correlated with the mutational load (the number of non-silent mutations) of the tumor: grade II diffuse gliomas harbour fewer genetic changes than grade III or IV, even within defined molecular subtypes (e.g. ATRX mutated diffuse gliomas). Conclusion We have identified PI3K mutations as novel prognostic markers in gliomas. We also demonstrate that the mutational load is associated with tumor grade. The increase in mutational load may partially explain the increased aggressiveness of higher grade diffuse gliomas when a subset of the affected genes actively contributes to gliomagenesis and/or progression.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Science
Education
Careers

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We see no obvious way the site makes money.

Not all websites are made for profit; some exist to inform or educate users. Or any other reason why people make websites. And this might be the case. Link.springer.com could have a money-making trick up its sleeve, but it's undetectable for now.

Keywords {🔍}

gliomas, grade, molecular, mutations, diffuse, survival, prognostic, tumor, genes, pubmed, article, analysis, google, scholar, table, glioma, tumors, data, idh, genetic, mutational, subtypes, cas, additional, load, classification, markers, mutated, identified, iii, patient, atrx, mutation, samples, age, idhwt, prognosis, astrocytomas, number, tcga, datasets, codeletion, file, patients, dataset, correlated, pikr, central, based, frequency,

Topics {✒️}

van den bent & pim article download pdf full size image neuropathology--haarlem consensus guidelines central nervous system 151 idh + atrx/tp53-mutated gliomas individual pi3-kinase mutations evidence-based diagnostic algorithm diffuse lower-grade gliomas perform log-rank tests idh-mutated diffuse gliomas identified pi3-kinase mutations tp53/atrx mutated gliomas grade ii/iii gliomas diaz jr la idh-mutated grade ii atrx/tp53 mutation status idh-wt diffuse gliomas entire chromosome/chromosomal arm atrx/tp53 mut tumors pi3-kinase pathway privacy choices/manage cookies natl cancer inst full access separated idh-mutated samples pi3-kinase mutations pi3 kinase mutations integrated genomic analysis low-frequency genes affect c-terminal domain creative commons license tert promoter mutations syngeneic glioma model adult malignant gliomas diffuse glioma patients lower grade glioma lipid kinase downstream receptor tyrosine kinases generated largely determines single molecular marker somatic genomic landscape genes chromosomes cancer determining 1p19q codeletion low grade glioma integrative genomic analysis classify diffuse gliomas small sample size article draaisma iii diffuse gliomas diffuse glioma stratified

Questions {❓}

Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:PI3 kinase mutations and mutational load as poor prognostic markers in diffuse glioma patients
         description:Recent advances in molecular diagnostics allow diffuse gliomas to be classified based on their genetic changes into distinct prognostic subtypes. However, a systematic analysis of all molecular markers has thus far not been performed; most classification schemes use a predefined and select set of genes/molecular markers. Here, we have analysed the TCGA dataset (combined glioblastoma (GBM) and lower grade glioma (LGG) datasets) to identify all prognostic genetic markers in diffuse gliomas in order to generate a comprehensive classification scheme. Of the molecular markers investigated (all genes mutated at a population frequency >1.7 % and frequent chromosomal imbalances) in the entire glioma dataset, 57 were significantly associated with overall survival. Of these, IDH1 or IDH2 mutations are associated with lowest hazard ratio, which confirms IDH as the most important prognostic marker in diffuse gliomas. Subsequent subgroup analysis largely confirms many of the currently used molecular classification schemes for diffuse gliomas (ATRX or TP53 mutations, 1p19q codeletion). Our analysis also identified PI3-kinase mutations as markers of poor prognosis in IDH-mutated + ATRX/TP53 mutated diffuse gliomas, median survival 3.7 v. 6.3 years (P = 0.02, Hazard rate (HR) 2.93, 95 % confidence interval (CI) 1.16 – 7.38). PI3-kinase mutations were also prognostic in two independent datasets. In our analysis, no additional molecular markers were identified that further refine the molecular classification of diffuse gliomas. Interestingly, these molecular classifiers do not fully explain the variability in survival observed for diffuse glioma patients. We demonstrate that tumor grade remains an important prognostic factor for overall survival in diffuse gliomas, even within molecular glioma subtypes. Tumor grade was correlated with the mutational load (the number of non-silent mutations) of the tumor: grade II diffuse gliomas harbour fewer genetic changes than grade III or IV, even within defined molecular subtypes (e.g. ATRX mutated diffuse gliomas). We have identified PI3K mutations as novel prognostic markers in gliomas. We also demonstrate that the mutational load is associated with tumor grade. The increase in mutational load may partially explain the increased aggressiveness of higher grade diffuse gliomas when a subset of the affected genes actively contributes to gliomagenesis and/or progression.
         datePublished:2015-12-23T00:00:00Z
         dateModified:2015-12-23T00:00:00Z
         pageStart:1
         pageEnd:11
         license:http://creativecommons.org/publicdomain/zero/1.0/
         sameAs:https://doi.org/10.1186/s40478-015-0265-4
         keywords:
            Diffuse glioma
            PIK3CA
            PIK3R1
            Mutational load
            Tumor grade
            IDH1
            IDH2
            1p19q codeletion
            ATRX
            TP53
            Neurosciences
            Pathology
            Neurology
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig1_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig2_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig3_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig4_HTML.gif
         isPartOf:
            name:Acta Neuropathologica Communications
            issn:
               2051-5960
            volumeNumber:3
            type:
               Periodical
               PublicationVolume
         publisher:
            name:BioMed Central
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Kaspar Draaisma
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Maarten M. J. Wijnenga
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Bas Weenink
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Ya Gao
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Marcel Smid
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:P. Robe
               affiliation:
                     name:UMC Utrecht
                     address:
                        name:Department of Neurosurgery, UMC Utrecht, Utrecht, Netherlands
                        type:PostalAddress
                     type:Organization
                     name:University of Liège
                     address:
                        name:Department of Human Genetics, University of Liège, Liège, Belgium
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Martin J. van den Bent
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Pim J. French
               affiliation:
                     name:Erasmus MC
                     address:
                        name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:1
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:PI3 kinase mutations and mutational load as poor prognostic markers in diffuse glioma patients
      description:Recent advances in molecular diagnostics allow diffuse gliomas to be classified based on their genetic changes into distinct prognostic subtypes. However, a systematic analysis of all molecular markers has thus far not been performed; most classification schemes use a predefined and select set of genes/molecular markers. Here, we have analysed the TCGA dataset (combined glioblastoma (GBM) and lower grade glioma (LGG) datasets) to identify all prognostic genetic markers in diffuse gliomas in order to generate a comprehensive classification scheme. Of the molecular markers investigated (all genes mutated at a population frequency >1.7 % and frequent chromosomal imbalances) in the entire glioma dataset, 57 were significantly associated with overall survival. Of these, IDH1 or IDH2 mutations are associated with lowest hazard ratio, which confirms IDH as the most important prognostic marker in diffuse gliomas. Subsequent subgroup analysis largely confirms many of the currently used molecular classification schemes for diffuse gliomas (ATRX or TP53 mutations, 1p19q codeletion). Our analysis also identified PI3-kinase mutations as markers of poor prognosis in IDH-mutated + ATRX/TP53 mutated diffuse gliomas, median survival 3.7 v. 6.3 years (P = 0.02, Hazard rate (HR) 2.93, 95 % confidence interval (CI) 1.16 – 7.38). PI3-kinase mutations were also prognostic in two independent datasets. In our analysis, no additional molecular markers were identified that further refine the molecular classification of diffuse gliomas. Interestingly, these molecular classifiers do not fully explain the variability in survival observed for diffuse glioma patients. We demonstrate that tumor grade remains an important prognostic factor for overall survival in diffuse gliomas, even within molecular glioma subtypes. Tumor grade was correlated with the mutational load (the number of non-silent mutations) of the tumor: grade II diffuse gliomas harbour fewer genetic changes than grade III or IV, even within defined molecular subtypes (e.g. ATRX mutated diffuse gliomas). We have identified PI3K mutations as novel prognostic markers in gliomas. We also demonstrate that the mutational load is associated with tumor grade. The increase in mutational load may partially explain the increased aggressiveness of higher grade diffuse gliomas when a subset of the affected genes actively contributes to gliomagenesis and/or progression.
      datePublished:2015-12-23T00:00:00Z
      dateModified:2015-12-23T00:00:00Z
      pageStart:1
      pageEnd:11
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s40478-015-0265-4
      keywords:
         Diffuse glioma
         PIK3CA
         PIK3R1
         Mutational load
         Tumor grade
         IDH1
         IDH2
         1p19q codeletion
         ATRX
         TP53
         Neurosciences
         Pathology
         Neurology
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig1_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig2_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig3_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs40478-015-0265-4/MediaObjects/40478_2015_265_Fig4_HTML.gif
      isPartOf:
         name:Acta Neuropathologica Communications
         issn:
            2051-5960
         volumeNumber:3
         type:
            Periodical
            PublicationVolume
      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Kaspar Draaisma
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Maarten M. J. Wijnenga
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Bas Weenink
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Ya Gao
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Marcel Smid
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:P. Robe
            affiliation:
                  name:UMC Utrecht
                  address:
                     name:Department of Neurosurgery, UMC Utrecht, Utrecht, Netherlands
                     type:PostalAddress
                  type:Organization
                  name:University of Liège
                  address:
                     name:Department of Human Genetics, University of Liège, Liège, Belgium
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Martin J. van den Bent
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Pim J. French
            affiliation:
                  name:Erasmus MC
                  address:
                     name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:1
["Periodical","PublicationVolume"]:
      name:Acta Neuropathologica Communications
      issn:
         2051-5960
      volumeNumber:3
Organization:
      name:BioMed Central
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:UMC Utrecht
      address:
         name:Department of Neurosurgery, UMC Utrecht, Utrecht, Netherlands
         type:PostalAddress
      name:University of Liège
      address:
         name:Department of Human Genetics, University of Liège, Liège, Belgium
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
      name:Erasmus MC
      address:
         name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Kaspar Draaisma
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Maarten M. J. Wijnenga
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Bas Weenink
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Ya Gao
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Marcel Smid
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:P. Robe
      affiliation:
            name:UMC Utrecht
            address:
               name:Department of Neurosurgery, UMC Utrecht, Utrecht, Netherlands
               type:PostalAddress
            type:Organization
            name:University of Liège
            address:
               name:Department of Human Genetics, University of Liège, Liège, Belgium
               type:PostalAddress
            type:Organization
      name:Martin J. van den Bent
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Pim J. French
      affiliation:
            name:Erasmus MC
            address:
               name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Neurosurgery, UMC Utrecht, Utrecht, Netherlands
      name:Department of Human Genetics, University of Liège, Liège, Belgium
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
      name:Department of Neurology, Erasmus MC, Rotterdam, The Netherlands

External Links {🔗}(170)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

5s.

LINK . SPRINGER . COM {}