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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in diagnoses of infiltrative glioma</title><author><name sortKey="Chen, Li" sort="Chen, Li" uniqKey="Chen L" first="Li" last="Chen">Li Chen</name></author><author><name sortKey="Voronovich, Zoya" sort="Voronovich, Zoya" uniqKey="Voronovich Z" first="Zoya" last="Voronovich">Zoya Voronovich</name></author><author><name sortKey="Clark, Kenneth" sort="Clark, Kenneth" uniqKey="Clark K" first="Kenneth" last="Clark">Kenneth Clark</name></author><author><name sortKey="Hands, Isaac" sort="Hands, Isaac" uniqKey="Hands I" first="Isaac" last="Hands">Isaac Hands</name></author><author><name sortKey="Mannas, Jonathan" sort="Mannas, Jonathan" uniqKey="Mannas J" first="Jonathan" last="Mannas">Jonathan Mannas</name></author><author><name sortKey="Walsh, Meggen" sort="Walsh, Meggen" uniqKey="Walsh M" first="Meggen" last="Walsh">Meggen Walsh</name></author><author><name sortKey="Nikiforova, Marina N" sort="Nikiforova, Marina N" uniqKey="Nikiforova M" first="Marina N." last="Nikiforova">Marina N. Nikiforova</name></author><author><name sortKey="Durbin, Eric B" sort="Durbin, Eric B" uniqKey="Durbin E" first="Eric B." last="Durbin">Eric B. Durbin</name></author><author><name sortKey="Weiss, Heidi" sort="Weiss, Heidi" uniqKey="Weiss H" first="Heidi" last="Weiss">Heidi Weiss</name></author><author><name sortKey="Horbinski, Craig" sort="Horbinski, Craig" uniqKey="Horbinski C" first="Craig" last="Horbinski">Craig Horbinski</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24860178</idno><idno type="pmc">4201069</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201069</idno><idno type="RBID">PMC:4201069</idno><idno type="doi">10.1093/neuonc/nou097</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000B61</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B61</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in diagnoses of infiltrative glioma</title><author><name sortKey="Chen, Li" sort="Chen, Li" uniqKey="Chen L" first="Li" last="Chen">Li Chen</name></author><author><name sortKey="Voronovich, Zoya" sort="Voronovich, Zoya" uniqKey="Voronovich Z" first="Zoya" last="Voronovich">Zoya Voronovich</name></author><author><name sortKey="Clark, Kenneth" sort="Clark, Kenneth" uniqKey="Clark K" first="Kenneth" last="Clark">Kenneth Clark</name></author><author><name sortKey="Hands, Isaac" sort="Hands, Isaac" uniqKey="Hands I" first="Isaac" last="Hands">Isaac Hands</name></author><author><name sortKey="Mannas, Jonathan" sort="Mannas, Jonathan" uniqKey="Mannas J" first="Jonathan" last="Mannas">Jonathan Mannas</name></author><author><name sortKey="Walsh, Meggen" sort="Walsh, Meggen" uniqKey="Walsh M" first="Meggen" last="Walsh">Meggen Walsh</name></author><author><name sortKey="Nikiforova, Marina N" sort="Nikiforova, Marina N" uniqKey="Nikiforova M" first="Marina N." last="Nikiforova">Marina N. Nikiforova</name></author><author><name sortKey="Durbin, Eric B" sort="Durbin, Eric B" uniqKey="Durbin E" first="Eric B." last="Durbin">Eric B. Durbin</name></author><author><name sortKey="Weiss, Heidi" sort="Weiss, Heidi" uniqKey="Weiss H" first="Heidi" last="Weiss">Heidi Weiss</name></author><author><name sortKey="Horbinski, Craig" sort="Horbinski, Craig" uniqKey="Horbinski C" first="Craig" last="Horbinski">Craig Horbinski</name></author></analytic><series><title level="j">Neuro-Oncology</title><idno type="ISSN">1522-8517</idno><idno type="eISSN">1523-5866</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Several variables are associated with the likelihood of isocitrate dehydrogenase 1 or 2 (<italic>IDH1/2</italic>) mutation in gliomas, though no guidelines yet exist for when testing is warranted, especially when an R132H IDH1 immunostain is negative.</p></sec><sec><title>Methods</title><p>A cohort of 89 patients was used to build <italic>IDH1/2</italic> mutation prediction models in World Health Organization grades II–IV gliomas, and an external cohort of 100 patients was used for validation. Logistic regression and backward model selection with the Akaike information criterion were used to develop prediction models.</p></sec><sec><title>Results</title><p>A multivariable model, incorporating patient age, glioblastoma multiforme diagnosis, and prior history of grade II or III glioma, was developed to predict <italic>IDH1/2</italic> mutation probability. This model generated an area under the curve (AUC) of 0.934 (95% CI: 0.878, 0.978) in the external validation cohort and 0.941 (95% CI: 0.918, 0.962) in the cohort of The Cancer Genome Atlas. When R132H IDH1 immunostain information was added, AUC increased to 0.986 (95% CI: 0.967, 0.998). This model had an AUC of 0.947 (95% CI: 0.891, 0.995) in predicting whether an R132H IDH1 immunonegative case harbored a less common <italic>IDH1</italic> or <italic>IDH2</italic> mutation. The models were also 94% accurate in predicting <italic>IDH1/2</italic> mutation status in gliomas from The Cancer Genome Atlas. An interactive web-based application for calculating the probability of an <italic>IDH1/2</italic> mutation is now available using these models.</p></sec><sec><title>Conclusions</title><p>We have integrated multiple variables to generate a probability of an <italic>IDH1/2</italic> mutation. The associated web-based application can help triage diffuse gliomas that would benefit from mutation testing in both clinical and research settings.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neuro Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Neuro-oncology</journal-id><journal-id journal-id-type="publisher-id">neuonc</journal-id><journal-id journal-id-type="hwp">neuonc</journal-id><journal-title-group><journal-title>Neuro-Oncology</journal-title></journal-title-group><issn pub-type="ppub">1522-8517</issn><issn pub-type="epub">1523-5866</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24860178</article-id><article-id pub-id-type="pmc">4201069</article-id><article-id pub-id-type="doi">10.1093/neuonc/nou097</article-id><article-id pub-id-type="publisher-id">nou097</article-id><article-categories><subj-group subj-group-type="heading"><subject>Basic and Translational Investigations</subject></subj-group></article-categories><title-group><article-title>Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in diagnoses of infiltrative glioma</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Li</given-names></name></contrib><contrib contrib-type="author"><name><surname>Voronovich</surname><given-names>Zoya</given-names></name></contrib><contrib contrib-type="author"><name><surname>Clark</surname><given-names>Kenneth</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hands</surname><given-names>Isaac</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mannas</surname><given-names>Jonathan</given-names></name></contrib><contrib contrib-type="author"><name><surname>Walsh</surname><given-names>Meggen</given-names></name></contrib><contrib contrib-type="author"><name><surname>Nikiforova</surname><given-names>Marina N.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Durbin</surname><given-names>Eric B.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Weiss</surname><given-names>Heidi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Horbinski</surname><given-names>Craig</given-names></name></contrib><aff><addr-line>Biostatistics Shared Resource Facility, Markey Cancer Center</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (L.C., H.W.);<addr-line>Department of Biostatistics, College of Public Health</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (L.C., H.W.);<addr-line>Department of Pathology</addr-line>,<institution>University of Pittsburgh</institution>,<addr-line>Pittsburgh, Pennsylvania</addr-line> (Z.V., K.C., M.N.N.);<addr-line>Cancer Research Informatics Shared Resource Facility, Markey Cancer Center</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (I.H., E.B.D.);<addr-line>Department of Neurosurgery</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (J.M.);<addr-line>Department of Pathology and Laboratory Medicine</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (M.W.);<addr-line>Division of Biomedical Informatics, Department of Biostatistics, College of Public Health</addr-line>,<institution>University of Kentucky</institution>,<addr-line>Lexington, Kentucky</addr-line> (E.B.D.)</aff></contrib-group><author-notes><corresp><bold>Corresponding Author:</bold> Craig Horbinski, MD, PhD, 307 Combs Building, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536 (<email>craig.horbinski@uky.edu</email>).</corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>23</day><month>5</month><year>2014</year></pub-date><volume>16</volume><issue>11</issue><fpage>1478</fpage><lpage>1483</lpage><history><date date-type="received"><day>7</day><month>11</month><year>2013</year></date><date date-type="accepted"><day>23</day><month>4</month><year>2014</year></date></history><permissions><copyright-statement>© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="nou097.pdf"></self-uri><abstract><sec><title>Background</title><p>Several variables are associated with the likelihood of isocitrate dehydrogenase 1 or 2 (<italic>IDH1/2</italic>) mutation in gliomas, though no guidelines yet exist for when testing is warranted, especially when an R132H IDH1 immunostain is negative.</p></sec><sec><title>Methods</title><p>A cohort of 89 patients was used to build <italic>IDH1/2</italic> mutation prediction models in World Health Organization grades II–IV gliomas, and an external cohort of 100 patients was used for validation. Logistic regression and backward model selection with the Akaike information criterion were used to develop prediction models.</p></sec><sec><title>Results</title><p>A multivariable model, incorporating patient age, glioblastoma multiforme diagnosis, and prior history of grade II or III glioma, was developed to predict <italic>IDH1/2</italic> mutation probability. This model generated an area under the curve (AUC) of 0.934 (95% CI: 0.878, 0.978) in the external validation cohort and 0.941 (95% CI: 0.918, 0.962) in the cohort of The Cancer Genome Atlas. When R132H IDH1 immunostain information was added, AUC increased to 0.986 (95% CI: 0.967, 0.998). This model had an AUC of 0.947 (95% CI: 0.891, 0.995) in predicting whether an R132H IDH1 immunonegative case harbored a less common <italic>IDH1</italic> or <italic>IDH2</italic> mutation. The models were also 94% accurate in predicting <italic>IDH1/2</italic> mutation status in gliomas from The Cancer Genome Atlas. An interactive web-based application for calculating the probability of an <italic>IDH1/2</italic> mutation is now available using these models.</p></sec><sec><title>Conclusions</title><p>We have integrated multiple variables to generate a probability of an <italic>IDH1/2</italic> mutation. The associated web-based application can help triage diffuse gliomas that would benefit from mutation testing in both clinical and research settings.</p></sec></abstract><kwd-group><kwd>glioma</kwd><kwd>IDH1</kwd><kwd>IDH2</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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