CNS5:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted: Difference between revisions
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{{DISPLAYTITLE:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted}} | {{DISPLAYTITLE:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted}} | ||
[[CNS5:Table_of_Contents|Central Nervous System Tumours(WHO Classification, 5th ed.)]] | |||
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]] | |||
{{Under Construction}} | {{Under Construction}} | ||
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Shashirekha Shetty, PhD, Director, Cytogenetics Laboratory, Center for Human Genetics Laboratory, University Hospitals | Shashirekha Shetty, PhD, Director, Cytogenetics Laboratory, Center for Human Genetics Laboratory, University Hospitals | ||
==WHO Classification of Disease== | ==WHO Classification of Disease== | ||
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|} | |} | ||
== | ==Related Terminology== | ||
{| class="wikitable" | {| class="wikitable" | ||
| | |+ | ||
| | |Acceptable | ||
|N/A | |||
| | |||
|- | |- | ||
| | |Not Recommended | ||
|Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted | |||
|} | |} | ||
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'''Add content below into table above''' | |||
- Oligodendrogliomas are defined by a t(1;19)(q10;p10) rearrangement that results in 1p/19q whole-arm codeletion | - Oligodendrogliomas are defined by a t(1;19)(q10;p10) rearrangement that results in 1p/19q whole-arm codeletion | ||
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|No | |No | ||
|1p/19q codeletion is the defining mutation of oligodendrogliomas and is required for diagnosis. Prognosis is dependent on histomorphologic grading<ref name=":6">{{Cite journal|last=Griffin|first=Constance A.|last2=Burger|first2=Peter|last3=Morsberger|first3=Laura|last4=Yonescu|first4=Raluca|last5=Swierczynski|first5=Sharon|last6=Weingart|first6=Jon D.|last7=Murphy|first7=Kathleen M.|date=2006-10|title=Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss|url=https://pubmed.ncbi.nlm.nih.gov/17021403|journal=Journal of Neuropathology and Experimental Neurology|volume=65|issue=10|pages=988–994|doi=10.1097/01.jnen.0000235122.98052.8f|issn=0022-3069|pmid=17021403}}</ref> <ref name=":7">{{Cite journal|last=Jenkins|first=Robert B.|last2=Blair|first2=Hilary|last3=Ballman|first3=Karla V.|last4=Giannini|first4=Caterina|last5=Arusell|first5=Robert M.|last6=Law|first6=Mark|last7=Flynn|first7=Heather|last8=Passe|first8=Sandra|last9=Felten|first9=Sara|date=2006-10-15|title=A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma|url=https://pubmed.ncbi.nlm.nih.gov/17047046|journal=Cancer Research|volume=66|issue=20|pages=9852–9861|doi=10.1158/0008-5472.CAN-06-1796|issn=0008-5472|pmid=17047046}}</ref> | |1p/19q codeletion is the defining mutation of oligodendrogliomas and is required for diagnosis. Prognosis is dependent on histomorphologic grading<ref name=":6">{{Cite journal|last=Griffin|first=Constance A.|last2=Burger|first2=Peter|last3=Morsberger|first3=Laura|last4=Yonescu|first4=Raluca|last5=Swierczynski|first5=Sharon|last6=Weingart|first6=Jon D.|last7=Murphy|first7=Kathleen M.|date=2006-10|title=Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss|url=https://pubmed.ncbi.nlm.nih.gov/17021403|journal=Journal of Neuropathology and Experimental Neurology|volume=65|issue=10|pages=988–994|doi=10.1097/01.jnen.0000235122.98052.8f|issn=0022-3069|pmid=17021403}}</ref> <ref name=":7">{{Cite journal|last=Jenkins|first=Robert B.|last2=Blair|first2=Hilary|last3=Ballman|first3=Karla V.|last4=Giannini|first4=Caterina|last5=Arusell|first5=Robert M.|last6=Law|first6=Mark|last7=Flynn|first7=Heather|last8=Passe|first8=Sandra|last9=Felten|first9=Sara|date=2006-10-15|title=A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma|url=https://pubmed.ncbi.nlm.nih.gov/17047046|journal=Cancer Research|volume=66|issue=20|pages=9852–9861|doi=10.1158/0008-5472.CAN-06-1796|issn=0008-5472|pmid=17047046}}</ref> | ||
|} | |} | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Chr #!! | !Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s) | ||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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'''Add content below into table above''' | |||
Put your text here and fill in the table | Put your text here and fill in the table | ||
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!Chromosomal Pattern | !Chromosomal Pattern | ||
!Molecular Pathogenesis | !Molecular Pathogenesis | ||
! | !Prevalence - | ||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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Put your text here | Put your text here | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene!! | !Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence - | ||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span>''EGFR'' | |<span class="blue-text">EXAMPLE:</span>''EGFR'' | ||
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Put your text here and fill in the table | Put your text here and fill in the table | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!! | !Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC / TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations | ||
! | !Diagnostic Significance (Yes, No or Unknown) | ||
!Prognostic Significance (Yes, No or Unknown) | !Prognostic Significance (Yes, No or Unknown) | ||
!Therapeutic Significance (Yes, No or Unknown) | !Therapeutic Significance (Yes, No or Unknown) | ||
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|} | |} | ||
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
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==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
<br /> | |||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
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|Induces accelerated cell proliferation<ref name=":17" /> | |Induces accelerated cell proliferation<ref name=":17" /> | ||
|} | |} | ||
==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
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==Familial Forms== | ==Familial Forms== | ||
- Germline mutations in ''POT1'' have been associated with familial oligodendroglioma<ref>{{Cite journal|last=Bainbridge|first=Matthew N.|last2=Armstrong|first2=Georgina N.|last3=Gramatges|first3=M. Monica|last4=Bertuch|first4=Alison A.|last5=Jhangiani|first5=Shalini N.|last6=Doddapaneni|first6=Harsha|last7=Lewis|first7=Lora|last8=Tombrello|first8=Joseph|last9=Tsavachidis|first9=Spyros|date=2015-01|title=Germline mutations in shelterin complex genes are associated with familial glioma|url=https://pubmed.ncbi.nlm.nih.gov/25482530|journal=Journal of the National Cancer Institute|volume=107|issue=1|pages=384|doi=10.1093/jnci/dju384|issn=1460-2105|pmc=4296199|pmid=25482530}}</ref> | - Germline mutations in ''POT1'' have been associated with familial oligodendroglioma<ref>{{Cite journal|last=Bainbridge|first=Matthew N.|last2=Armstrong|first2=Georgina N.|last3=Gramatges|first3=M. Monica|last4=Bertuch|first4=Alison A.|last5=Jhangiani|first5=Shalini N.|last6=Doddapaneni|first6=Harsha|last7=Lewis|first7=Lora|last8=Tombrello|first8=Joseph|last9=Tsavachidis|first9=Spyros|date=2015-01|title=Germline mutations in shelterin complex genes are associated with familial glioma|url=https://pubmed.ncbi.nlm.nih.gov/25482530|journal=Journal of the National Cancer Institute|volume=107|issue=1|pages=384|doi=10.1093/jnci/dju384|issn=1460-2105|pmc=4296199|pmid=25482530}}</ref> | ||
==Additional Information== | |||
This disease is <u>defined/characterized</u> as detailed below: | |||
*Can be called anaplastic oligodendroglioma (historical; now known as oligodendroglioma, IDH-mutant and 1p/19q-codeleted, CNS WHO grade 3). It is discouraged to call this entity oligoastrocytoma (oligodendroglioma and astrocytoma are molecularly distinct entities. The diagnosis is reserved for rare cases where a dual genotype is identified, or where molecular testing could not be completed). | |||
*A molecularly defined diffusely infiltrating glioma with IDH1 or IDH2 mutation and codeletion of chromosome arms 1p and 19q<ref name=":0">WHO Classification of Tumours Editorial Board. Central nervous system tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 6). <nowiki>https://publications.iarc.fr/601</nowiki>.</ref> . | |||
*Oligodendrogliomas are graded morphologically as either CNS WHO grade 2 or CNS WHO grade 3. | |||
*In rare cases where molecular studies are unable to be completed or have failed, tumors can be histologically diagnosed as Oligodendroglioma, NOS (not otherwise specified). | |||
The <u>epidemiology/prevalence</u> of this disease is detailed below: | |||
*Epidemiological statistics should be interpreted with caution as oligodendroglioma is now molecularly defined. | |||
**A subset of tumor historically diagnosed as oligodendroglioma on morphological grounds may therefore not meet current definition | |||
*Oligodendrogliomas occur primarily in adults (median age 43 years for CNS WHO grade 2 and 50 years for CNS WHO grade 3)<ref name=":1">{{Cite journal|last=Ostrom|first=Quinn T.|last2=Cioffi|first2=Gino|last3=Gittleman|first3=Haley|last4=Patil|first4=Nirav|last5=Waite|first5=Kristin|last6=Kruchko|first6=Carol|last7=Barnholtz-Sloan|first7=Jill S.|date=2019-11-01|title=CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016|url=https://pubmed.ncbi.nlm.nih.gov/31675094|journal=Neuro-Oncology|volume=21|issue=Suppl 5|pages=v1–v100|doi=10.1093/neuonc/noz150|issn=1523-5866|pmc=6823730|pmid=31675094}}</ref> | |||
**Slight male preponderance (M:F = 1.2:1<ref name=":1" />) | |||
*Low incidence worldwide | |||
**Incidence is changing over time due to refined molecular definition | |||
***Incidence rate (cases per 100,000 person-years) for histologically defined oligodendroglioma – 0.10% (Republic of Korea; <ref name=":2">{{Cite journal|last=Lee|first=Chang-Hyun|last2=Jung|first2=Kyu-Won|last3=Yoo|first3=Heon|last4=Park|first4=Sohee|last5=Lee|first5=Seung Hoon|date=2010-08|title=Epidemiology of primary brain and central nervous system tumors in Korea|url=https://pubmed.ncbi.nlm.nih.gov/20856664|journal=Journal of Korean Neurosurgical Society|volume=48|issue=2|pages=145–152|doi=10.3340/jkns.2010.48.2.145|issn=1598-7876|pmc=2941858|pmid=20856664}}</ref>), 0.50 (France <ref name=":3">{{Cite journal|last=Darlix|first=Amélie|last2=Zouaoui|first2=Sonia|last3=Rigau|first3=Valérie|last4=Bessaoud|first4=Faiza|last5=Figarella-Branger|first5=Dominique|last6=Mathieu-Daudé|first6=Hélène|last7=Trétarre|first7=Brigitte|last8=Bauchet|first8=Fabienne|last9=Duffau|first9=Hugues|date=2017-02|title=Epidemiology for primary brain tumors: a nationwide population-based study|url=https://pubmed.ncbi.nlm.nih.gov/27853959|journal=Journal of Neuro-Oncology|volume=131|issue=3|pages=525–546|doi=10.1007/s11060-016-2318-3|issn=1573-7373|pmid=27853959}}</ref>), 0.23 (USA 31675094<ref name=":1" />) | |||
***Incidence rate for histologically defined CNS WHO Grade 3 oligodendroglioma – 0.06% (Republic of Korea<ref name=":2" />), 0.39 (France <ref name=":3" />), 0.11 (USA<ref name=":1" />) | |||
**CNS WHO grade 2 oligodendrogliomas account for 0.9% of primary brain tumors in US (PMID: 34608945)<ref name=":1" /> | |||
**CNS WHO grade 3 oligodendrogliomas account of primary brain tumors in the US(PMID: 34608945)<ref name=":1" /> | |||
The <u>clinical features</u> of this disease are detailed below: | |||
Oligodendrogliomas are most often low-grade, slow growing tumors | |||
*Tumors are frequently asymptomatic and are increasingly found incidentally on imaging for other indications<ref name=":20">{{Cite journal|last=Wijnenga|first=Maarten M. J.|last2=French|first2=Pim J.|last3=Dubbink|first3=Hendrikus J.|last4=Dinjens|first4=Winand N. M.|last5=Atmodimedjo|first5=Peggy N.|last6=Kros|first6=Johan M.|last7=Smits|first7=Marion|last8=Gahrmann|first8=Renske|last9=Rutten|first9=Geert-Jan|date=2018-01-10|title=The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis|url=https://pubmed.ncbi.nlm.nih.gov/29016833|journal=Neuro-Oncology|volume=20|issue=1|pages=103–112|doi=10.1093/neuonc/nox176|issn=1523-5866|pmc=5761503|pmid=29016833}}</ref> | |||
*Most commonly present with seizures<ref name=":4">{{Cite journal|last=Zetterling|first=Maria|last2=Berhane|first2=Luwam|last3=Alafuzoff|first3=Irina|last4=Jakola|first4=Asgeir S.|last5=Smits|first5=Anja|date=2017|title=Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases|url=https://pubmed.ncbi.nlm.nih.gov/29186201|journal=PloS One|volume=12|issue=11|pages=e0188419|doi=10.1371/journal.pone.0188419|issn=1932-6203|pmc=5706698|pmid=29186201}}</ref> | |||
*Can present with focal neurologic deficits or cognitive changes secondary to increased cranial pressure, especially in the high-grade setting<ref name=":4" /> | |||
*Signs and symptoms - Seizures<ref name=":4" />; Headache; Signs of increased intracranial pressure (Focal neurologic deficits, Cognitive changes); Asymptomatic (increasingly an incidental finding on neuroimaging<ref name=":4" />) | |||
*Laboratory findings - Not applicable | |||
The <u>sites of involvement</u> of this disease are detailed below: | |||
*Approximately 60% of oligodendrogliomas occur within the frontal lobes with | |||
**14-16% in the temporal lobe | |||
**10-15% in the parietal lobe | |||
**1-6% in the occipital lobe | |||
**Less commonly basal ganglia / cerebellum brainstem | |||
*Leptomeningeal spread and gliomatosis cerebri pattern can rarely occur | |||
*Rare spinal lesions have been reported but lack genotyping to confirm true oligodendroglioma | |||
*Extracranial metastasis exceedingly rare (CNS WHO grade 3) | |||
The <u>morphologic features</u> of this disease are detailed below: | |||
*Classically consist of cells with round, monomorphous nuclei with stippled chromatin and perinuclear halos (artifactual fried-egg appearance) | |||
**Intervening delicate “chicken wire” vasculature | |||
**Can contain GFAP-positive minigemistocytes | |||
**Often contain microcalcifications, especially in low-grade tumors<ref name=":0" /> | |||
The <u>immunophenotype</u> of this disease is detailed below: | |||
*Positive (universal) - Retained nuclear ATRX<ref name=":5">{{Cite journal|last=Liu|first=Xiao-Yang|last2=Gerges|first2=Noha|last3=Korshunov|first3=Andrey|last4=Sabha|first4=Nesrin|last5=Khuong-Quang|first5=Dong-Anh|last6=Fontebasso|first6=Adam M.|last7=Fleming|first7=Adam|last8=Hadjadj|first8=Djihad|last9=Schwartzentruber|first9=Jeremy|date=2012-11|title=Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations|url=https://pubmed.ncbi.nlm.nih.gov/22886134|journal=Acta Neuropathologica|volume=124|issue=5|pages=615–625|doi=10.1007/s00401-012-1031-3|issn=1432-0533|pmid=22886134}}</ref>, OLIG2<ref name=":21">{{Cite journal|last=Ligon|first=Keith L.|last2=Alberta|first2=John A.|last3=Kho|first3=Alvin T.|last4=Weiss|first4=Jennifer|last5=Kwaan|first5=Mary R.|last6=Nutt|first6=Catherine L.|last7=Louis|first7=David N.|last8=Stiles|first8=Charles D.|last9=Rowitch|first9=David H.|date=2004-05|title=The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas|url=https://pubmed.ncbi.nlm.nih.gov/15198128|journal=Journal of Neuropathology and Experimental Neurology|volume=63|issue=5|pages=499–509|doi=10.1093/jnen/63.5.499|issn=0022-3069|pmid=15198128}}</ref>, S100<ref name=":22">{{Cite journal|last=Reifenberger|first=G.|last2=Szymas|first2=J.|last3=Wechsler|first3=W.|date=1987|title=Differential expression of glial- and neuronal-associated antigens in human tumors of the central and peripheral nervous system|url=https://pubmed.ncbi.nlm.nih.gov/3314309|journal=Acta Neuropathologica|volume=74|issue=2|pages=105–123|doi=10.1007/BF00692841|issn=0001-6322|pmid=3314309}}</ref>, MAP2<ref name=":23">{{Cite journal|last=Blümcke|first=I.|last2=Becker|first2=A. J.|last3=Normann|first3=S.|last4=Hans|first4=V.|last5=Riederer|first5=B. M.|last6=Krajewski|first6=S.|last7=Wiestler|first7=O. D.|last8=Reifenberger|first8=G.|date=2001-10|title=Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells|url=https://pubmed.ncbi.nlm.nih.gov/11589429|journal=Journal of Neuropathology and Experimental Neurology|volume=60|issue=10|pages=984–993|doi=10.1093/jnen/60.10.984|issn=0022-3069|pmid=11589429}}</ref>, SOX10<ref name=":24">{{Cite journal|last=Bannykh|first=Sergei I.|last2=Stolt|first2=C. Claus|last3=Kim|first3=Jung|last4=Perry|first4=Arie|last5=Wegner|first5=Michael|date=2006-01|title=Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas|url=https://pubmed.ncbi.nlm.nih.gov/16205963|journal=Journal of Neuro-Oncology|volume=76|issue=2|pages=115–127|doi=10.1007/s11060-005-5533-x|issn=0167-594X|pmid=16205963}}</ref> | |||
*Positive (subset) - Most positive for IDH1 p.R132H mutation (smaller subset lacking staining have non-canonical IDH mutation, <10%)<ref name=":25">{{Cite journal|last=Capper|first=David|last2=Zentgraf|first2=Hanswalter|last3=Balss|first3=Jörg|last4=Hartmann|first4=Christian|last5=von Deimling|first5=Andreas|date=2009-11|title=Monoclonal antibody specific for IDH1 R132H mutation|url=https://pubmed.ncbi.nlm.nih.gov/19798509|journal=Acta Neuropathologica|volume=118|issue=5|pages=599–601|doi=10.1007/s00401-009-0595-z|issn=1432-0533|pmid=19798509}}</ref>, Synaptophysin (cytoplasmic dot-like pattern<ref name=":26">{{Cite journal|last=Perry|first=Arie|last2=Burton|first2=Stephanie S.|last3=Fuller|first3=Gregory N.|last4=Robinson|first4=Christopher A.|last5=Palmer|first5=Cheryl A.|last6=Resch|first6=Lothar|last7=Bigio|first7=Eileen H.|last8=Gujrati|first8=Meena|last9=Rosenblum|first9=Marc K.|date=2010-08|title=Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall|url=https://pubmed.ncbi.nlm.nih.gov/20464403|journal=Acta Neuropathologica|volume=120|issue=2|pages=237–252|doi=10.1007/s00401-010-0695-9|issn=1432-0533|pmc=2892612|pmid=20464403}}</ref>) | |||
*Negative (universal) - Lack diffuse p53<ref name=":5" /> | |||
*Negative (subset) - N/A | |||
==Links== | ==Links== | ||
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Prior Author(s): | Prior Author(s): | ||
<nowiki>*</nowiki>''Citation of this Page'': “Oligodendroglioma, IDH-mutant and 1p/19q-codeleted”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted</nowiki>. | <nowiki>*</nowiki>''Citation of this Page'': “Oligodendroglioma, IDH-mutant and 1p/19q-codeleted”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted</nowiki>. | ||
[[Category:CNS5]][[Category:DISEASE]][[Category:Diseases O]] | [[Category:CNS5]] | ||
[[Category:DISEASE]] | |||
[[Category:Diseases O]] | |||