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.)]]


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{{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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|}


==Definition / Description of Disease==
==Related Terminology==
 
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).
 
==Synonyms / Terminology==
 
Anaplastic oligodendroglioma (historical; now known as oligodendroglioma, IDH-mutant and 1p/19q-codeleted, CNS WHO grade 3).
 
Oligoastrocytoma (discouraged; 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).
 
==Epidemiology / Prevalence==


-         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" />
==Clinical Features==
-         Oligodendrogliomas are most often low-grade, slow growing tumors
*  Tumors are frequently asymptomatic and are increasingly found incidentally on imaging for other indications<ref>{{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" />
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|Seizures<ref name=":4" />
|Acceptable
 
|N/A
Headache
 
Signs  of increased intracranial pressure
 
-          Focal neurologic deficits
 
-          Cognitive changes
 
Asymptomatic
 
-          Increasingly an incidental finding  on neuroimaging (PMID: 29186201)
|-
|'''Laboratory Findings'''
|Not  applicable
|}
 
==Sites of Involvement==
 
-         Approximately 60% of oligodendrogliomas occur within the frontal lobes with<ref name=":0" /><ref name=":1" />
 
*  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<ref>{{Cite journal|last=Andersen|first=Brian M.|last2=Miranda|first2=Caroline|last3=Hatzoglou|first3=Vaios|last4=DeAngelis|first4=Lisa M.|last5=Miller|first5=Alexandra M.|date=2019-05-21|title=Leptomeningeal metastases in glioma: The Memorial Sloan Kettering Cancer Center experience|url=https://pubmed.ncbi.nlm.nih.gov/31019097|journal=Neurology|volume=92|issue=21|pages=e2483–e2491|doi=10.1212/WNL.0000000000007529|issn=1526-632X|pmc=6541431|pmid=31019097}}</ref> <ref>{{Cite journal|last=Herrlinger|first=Ulrich|last2=Jones|first2=David T. W.|last3=Glas|first3=Martin|last4=Hattingen|first4=Elke|last5=Gramatzki|first5=Dorothee|last6=Stuplich|first6=Moritz|last7=Felsberg|first7=Jörg|last8=Bähr|first8=Oliver|last9=Gielen|first9=Gerrit H.|date=2016-02|title=Gliomatosis cerebri: no evidence for a separate brain tumor entity|url=https://pubmed.ncbi.nlm.nih.gov/26493382|journal=Acta Neuropathologica|volume=131|issue=2|pages=309–319|doi=10.1007/s00401-015-1495-z|issn=1432-0533|pmid=26493382}}</ref>
 
-         Rare spinal lesions have been reported but lack genotyping to confirm true oligodendroglioma<ref>{{Cite journal|last=Fountas|first=Kostas N.|last2=Karampelas|first2=Ioannis|last3=Nikolakakos|first3=Leonidas G.|last4=Troup|first4=E. Christopher|last5=Robinson|first5=Joe Sam|date=2005-02|title=Primary spinal cord oligodendroglioma: case report and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/15138790|journal=Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery|volume=21|issue=2|pages=171–175|doi=10.1007/s00381-004-0973-8|issn=0256-7040|pmid=15138790}}</ref> <ref>{{Cite journal|last=Hasturk|first=Askin Esen|last2=Gokce|first2=Emre Cemal|last3=Elbir|first3=Cagri|last4=Gel|first4=Gulce|last5=Canbay|first5=Suat|date=2017|title=A very rare spinal cord tumor primary spinal oligodendroglioma: A review of sixty cases in the literature|url=https://pubmed.ncbi.nlm.nih.gov/29021677|journal=Journal of Craniovertebral Junction & Spine|volume=8|issue=3|pages=253–262|doi=10.4103/jcvjs.JCVJS_1_17|issn=0974-8237|pmc=5634112|pmid=29021677}}</ref>
 
-         Extracranial metastasis exceedingly rare (CNS WHO grade 3)<ref>{{Cite journal|last=Merrell|first=Ryan|last2=Nabors|first2=L. Burton|last3=Perry|first3=Arie|last4=Palmer|first4=Cheryl Ann|date=2006-11|title=1p/19q chromosome deletions in metastatic oligodendroglioma|url=https://pubmed.ncbi.nlm.nih.gov/16710746|journal=Journal of Neuro-Oncology|volume=80|issue=2|pages=203–207|doi=10.1007/s11060-006-9179-0|issn=0167-594X|pmid=16710746}}</ref> <ref>{{Cite journal|last=Singh|first=Vikas K.|last2=Singh|first2=Shipra|last3=Bhupalam|first3=Leela|date=2019-07|title=Anaplastic oligodendroglioma metastasizing to the bone marrow: a unique case report and literature review|url=https://pubmed.ncbi.nlm.nih.gov/30526175|journal=The International Journal of Neuroscience|volume=129|issue=7|pages=722–728|doi=10.1080/00207454.2018.1557165|issn=1563-5279|pmid=30526175}}</ref> <ref>{{Cite journal|last=Burgy|first=Mickaël|last2=Chenard|first2=Marie-Pierre|last3=Noël|first3=Georges|last4=Bourahla|first4=Khalil|last5=Schott|first5=Roland|date=2019-06-28|title=Bone metastases from a 1p/19q codeleted and IDH1-mutant anaplastic oligodendroglioma: a case report|url=https://pubmed.ncbi.nlm.nih.gov/31248444|journal=Journal of Medical Case Reports|volume=13|issue=1|pages=202|doi=10.1186/s13256-019-2061-4|issn=1752-1947|pmc=6598291|pmid=31248444}}</ref>
 
==Morphologic Features==
 
-         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" />
 
==Immunophenotype==
 
<br />
 
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|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>{{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>{{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>{{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>{{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>{{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>{{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
|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 #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!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'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!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'''
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!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!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'''
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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|<span class="blue-text">EXAMPLE:</span>''EGFR''
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'''Add content below into table above'''
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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!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)'''
!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==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
<br />
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
|
|
|
|}
 
 
 
 
Put your text here and fill in the table
{| 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]]