@@ Line 1: / Line 1: @@
+{{DISPLAYTITLE:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted}}
+[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]
+{{Under Construction}}
+<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
 ==Primary Author(s)*==
@@ Line 5: / Line 12: @@
 Shashirekha Shetty, PhD, Director, Cytogenetics Laboratory, Center for Human Genetics Laboratory, University Hospitals
-__TOC__
+==WHO Classification of Disease==
-==Cancer Category/Type==
+{| class="wikitable"
+!Structure
+!Disease
+|-
+|Book
+|Central Nervous System Tumours (5th ed.)
+|-
+|Category
+|Gliomas, glioneuronal tumours, and neuronal tumours
+|-
+|Family
+|Gliomas, glioneuronal tumours, and neuronal tumours
+|-
+|Type
+|Adult-type diffuse gliomas
+|-
+|Subtype(s)
+|Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
+|}
-Central nervous system – Diffuse gliomas
+==Related Terminology==
-==Cancer Sub-Classification / Subtype==
-Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
-==Definition / Description of Disease==
-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"
-|'''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 Recommended
-|Not  applicable
+|Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted
 |}
-==Sites of Involvement==
+==Gene Rearrangements==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
--         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
+!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
+!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
 |-
-|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>
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|<span class="blue-text">EXAMPLE:</span>
+The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
 |-
-|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>
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
+|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
+|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
+|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
+|<span class="blue-text">EXAMPLE:</span> D
+|
+|<span class="blue-text">EXAMPLE:</span>
-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>)
+''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
 |-
-|Negative (universal)||Lack diffuse p53<ref name=":5" />
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
+|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
+Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Both balanced and unbalanced forms are observed by FISH (add references).
 |-
-|Negative (subset)||N/A
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|
 |}
-==Chromosomal Rearrangements (Gene Fusions)==
+'''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
-*   This alteration is now required to make the diagnosis of oligodendroglioma
+*  This alteration is now required to make the diagnosis of oligodendroglioma
 {| class="wikitable sortable"
@@ Line 146: / Line 128: @@
 |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>
 |}
 ==Individual Region Genomic Gain/Loss/LOH==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
+{| class="wikitable sortable"
+|-
+!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> Loss
+|<span class="blue-text">EXAMPLE:</span>
+chr7
+|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|<span class="blue-text">EXAMPLE:</span> No
+|<span class="blue-text">EXAMPLE:</span>
+Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Gain
+|<span class="blue-text">EXAMPLE:</span>
+chr8
+|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|<span class="blue-text">EXAMPLE:</span>
+Common recurrent secondary finding for t(8;21) (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
+|<span class="blue-text">EXAMPLE:</span>
+''ERBB2''
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
+|-
+|
+|
+|
+|
+|
+|
+|
+|}
+'''Add content below into table above'''
 Put your text here and fill in the table
@@ Line 171: / Line 209: @@
 |Loss CDKN2A gene locus associated with shorter  survival of grade 3<ref>{{Cite journal|last=Fallon|first=Kenneth B.|last2=Palmer|first2=Cheryl A.|last3=Roth|first3=Kevin A.|last4=Nabors|first4=L. Burton|last5=Wang|first5=Wenquan|last6=Carpenter|first6=Mark|last7=Banerjee|first7=Ruma|last8=Forsyth|first8=Peter|last9=Rich|first9=Keith|date=2004-04|title=Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas|url=https://pubmed.ncbi.nlm.nih.gov/15099021|journal=Journal of Neuropathology and Experimental Neurology|volume=63|issue=4|pages=314–322|doi=10.1093/jnen/63.4.314|issn=0022-3069|pmid=15099021}}</ref> <ref>{{Cite journal|last=Alentorn|first=Agustí|last2=Dehais|first2=Caroline|last3=Ducray|first3=François|last4=Carpentier|first4=Catherine|last5=Mokhtari|first5=Karima|last6=Figarella-Branger|first6=Dominique|last7=Chinot|first7=Olivier|last8=Cohen-Moyal|first8=Elisabeth|last9=Ramirez|first9=Carole|date=2015-10-13|title=Allelic loss of 9p21.3 is a prognostic factor in 1p/19q codeleted anaplastic gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26385879|journal=Neurology|volume=85|issue=15|pages=1325–1331|doi=10.1212/WNL.0000000000002014|issn=1526-632X|pmc=4617162|pmid=26385879}}</ref>
 |}
-==Characteristic Chromosomal Patterns==
+==Characteristic Chromosomal or Other Global Mutational Patterns==
+Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
+{| class="wikitable sortable"
+|-
+!Chromosomal Pattern
+!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>
+Co-deletion of 1p and 18q
+|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Microsatellite instability - hypermutated
+|
+|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
+|<span class="blue-text">EXAMPLE:</span> P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|}
+'''Add content below into table above'''
 Put your text here
@@ Line 189: / Line 266: @@
 |See  chromosomal rearrangements table - this pattern is due to an unbalanced  derivative translocation associated with oligodendroglioma<ref name=":6" /> <ref name=":7" /> <ref>{{Cite journal|last=Wesseling|first=Pieter|last2=van den Bent|first2=Martin|last3=Perry|first3=Arie|date=2015-06|title=Oligodendroglioma: pathology, molecular mechanisms and markers|url=https://pubmed.ncbi.nlm.nih.gov/25943885|journal=Acta Neuropathologica|volume=129|issue=6|pages=809–827|doi=10.1007/s00401-015-1424-1|issn=1432-0533|pmc=4436696|pmid=25943885}}</ref>
 |}
 ==Gene Mutations (SNV/INDEL)==
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
+{| class="wikitable sortable"
+|-
+!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''
+<br />
+|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
+|<span class="blue-text">EXAMPLE:</span> T
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
+|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
+<br />
+|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
+|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
+|<span class="blue-text">EXAMPLE:</span> P
+|
+|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
+'''Add content below into table above'''
 Put your text here and fill in the table
 {| 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)
 !Therapeutic Significance (Yes, No or Unknown)
@@ Line 213: / Line 339: @@
 |''TERT'' promoter <ref name=":11">{{Cite journal|last=Arita|first=Hideyuki|last2=Narita|first2=Yoshitaka|last3=Fukushima|first3=Shintaro|last4=Tateishi|first4=Kensuke|last5=Matsushita|first5=Yuko|last6=Yoshida|first6=Akihiko|last7=Miyakita|first7=Yasuji|last8=Ohno|first8=Makoto|last9=Collins|first9=V. Peter|date=2013-08|title=Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss|url=https://pubmed.ncbi.nlm.nih.gov/23764841|journal=Acta Neuropathologica|volume=126|issue=2|pages=267–276|doi=10.1007/s00401-013-1141-6|issn=1432-0533|pmid=23764841}}</ref> <ref name=":12">{{Cite journal|last=Killela|first=Patrick J.|last2=Reitman|first2=Zachary J.|last3=Jiao|first3=Yuchen|last4=Bettegowda|first4=Chetan|last5=Agrawal|first5=Nishant|last6=Diaz|first6=Luis A.|last7=Friedman|first7=Allan H.|last8=Friedman|first8=Henry|last9=Gallia|first9=Gary L.|date=2013-04-09|title=TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal|url=https://pubmed.ncbi.nlm.nih.gov/23530248|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=15|pages=6021–6026|doi=10.1073/pnas.1303607110|issn=1091-6490|pmc=3625331|pmid=23530248}}</ref> <ref name=":13">{{Cite journal|last=Koelsche|first=Christian|last2=Sahm|first2=Felix|last3=Capper|first3=David|last4=Reuss|first4=David|last5=Sturm|first5=Dominik|last6=Jones|first6=David T. W.|last7=Kool|first7=Marcel|last8=Northcott|first8=Paul A.|last9=Wiestler|first9=Benedikt|date=2013-12|title=Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system|url=https://pubmed.ncbi.nlm.nih.gov/24154961|journal=Acta Neuropathologica|volume=126|issue=6|pages=907–915|doi=10.1007/s00401-013-1195-5|issn=1432-0533|pmid=24154961}}</ref>
 |Oncogene
 |97%<ref>{{Cite journal|last=Lee|first=Yujin|last2=Koh|first2=Jaemoon|last3=Kim|first3=Seong-Ik|last4=Won|first4=Jae Kyung|last5=Park|first5=Chul-Kee|last6=Choi|first6=Seung Hong|last7=Park|first7=Sung-Hye|date=2017-08-29|title=The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas|url=https://pubmed.ncbi.nlm.nih.gov/28851427|journal=Acta Neuropathologica Communications|volume=5|issue=1|pages=62|doi=10.1186/s40478-017-0465-1|issn=2051-5960|pmc=5574236|pmid=28851427}}</ref>
 |
 |N/A
@@ Line 219: / Line 345: @@
 |Yes, favorable<ref>{{Cite journal|last=Arita|first=Hideyuki|last2=Matsushita|first2=Yuko|last3=Machida|first3=Ryunosuke|last4=Yamasaki|first4=Kai|last5=Hata|first5=Nobuhiro|last6=Ohno|first6=Makoto|last7=Yamaguchi|first7=Shigeru|last8=Sasayama|first8=Takashi|last9=Tanaka|first9=Shota|date=2020-11-23|title=TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations|url=https://pubmed.ncbi.nlm.nih.gov/33228806|journal=Acta Neuropathologica Communications|volume=8|issue=1|pages=201|doi=10.1186/s40478-020-01078-2|issn=2051-5960|pmc=7685625|pmid=33228806}}</ref>
 |No
 |Teenagers lack ''TERT'' promoter mutations<ref>{{Cite journal|last=Lee|first=Julieann|last2=Putnam|first2=Angelica R.|last3=Chesier|first3=Samuel H.|last4=Banerjee|first4=Anuradha|last5=Raffel|first5=Corey|last6=Van Ziffle|first6=Jessica|last7=Onodera|first7=Courtney|last8=Grenert|first8=James P.|last9=Bastian|first9=Boris C.|date=2018-09-19|title=Oligodendrogliomas, IDH-mutant and 1p/19q-codeleted, arising during teenage years often lack TERT promoter mutation that is typical of their adult counterparts|url=https://pubmed.ncbi.nlm.nih.gov/30231927|journal=Acta Neuropathologica Communications|volume=6|issue=1|pages=95|doi=10.1186/s40478-018-0598-x|issn=2051-5960|pmc=6145350|pmid=30231927}}</ref>
 |-
 |''CIC''
@@ Line 233: / Line 359: @@
 |Yes
 |No
 |Recurrent missense mutations in HMG-box  DNA-binding domain (exon 5) and C1 motif (exon 20) unique to oligodendro-glioma<ref>{{Cite journal|last=LeBlanc|first=Veronique G.|last2=Firme|first2=Marlo|last3=Song|first3=Jungeun|last4=Chan|first4=Susanna Y.|last5=Lee|first5=Min Hye|last6=Yip|first6=Stephen|last7=Chittaranjan|first7=Suganthi|last8=Marra|first8=Marco A.|date=2017-06|title=Comparative transcriptome analysis of isogenic cell line models and primary cancers links capicua (CIC) loss to activation of the MAPK signalling cascade|url=https://pubmed.ncbi.nlm.nih.gov/28295365|journal=The Journal of Pathology|volume=242|issue=2|pages=206–220|doi=10.1002/path.4894|issn=1096-9896|pmc=5485162|pmid=28295365}}</ref>. Shorter time to recurrence with concomintant ''FUBP1''  mut.<ref name=":14">{{Cite journal|last=Chan|first=Aden Ka-Yin|last2=Pang|first2=Jesse Chung-Sean|last3=Chung|first3=Nellie Yuk-Fei|last4=Li|first4=Kay Ka-Wai|last5=Poon|first5=Wai Sang|last6=Chan|first6=Danny Tat-Ming|last7=Shi|first7=Zhifeng|last8=Chen|first8=Liang|last9=Zhou|first9=Liangfu|date=2014-03|title=Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors|url=https://pubmed.ncbi.nlm.nih.gov/24030748|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=27|issue=3|pages=332–342|doi=10.1038/modpathol.2013.165|issn=1530-0285|pmid=24030748}}</ref>
 |-
 |''FUBP1''<ref name=":15">{{Cite journal|last=Sahm|first=Felix|last2=Koelsche|first2=Christian|last3=Meyer|first3=Jochen|last4=Pusch|first4=Stefan|last5=Lindenberg|first5=Kerstin|last6=Mueller|first6=Wolf|last7=Herold-Mende|first7=Christel|last8=von Deimling|first8=Andreas|last9=Hartmann|first9=Christian|date=2012-06|title=CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/22588899|journal=Acta Neuropathologica|volume=123|issue=6|pages=853–860|doi=10.1007/s00401-012-0993-5|issn=1432-0533|pmid=22588899}}</ref> <ref name=":16">{{Cite journal|last=Bettegowda|first=Chetan|last2=Agrawal|first2=Nishant|last3=Jiao|first3=Yuchen|last4=Sausen|first4=Mark|last5=Wood|first5=Laura D.|last6=Hruban|first6=Ralph H.|last7=Rodriguez|first7=Fausto J.|last8=Cahill|first8=Daniel P.|last9=McLendon|first9=Roger|date=2011-09-09|title=Mutations in CIC and FUBP1 contribute to human oligodendroglioma|url=https://pubmed.ncbi.nlm.nih.gov/21817013|journal=Science (New York, N.Y.)|volume=333|issue=6048|pages=1453–1455|doi=10.1126/science.1210557|issn=1095-9203|pmc=3170506|pmid=21817013}}</ref>
@@ Line 241: / Line 367: @@
 % grade 3
 -30%<ref name=":16" />
 |
 |N/A
@@ Line 247: / Line 373: @@
 |Yes
 |No
 |Shorter time to recurrence with concomitant  ''CIC'' mut.<ref name=":14" />
 |-
 |''NOTCH1'' <ref>{{Cite journal|last=Suzuki|first=Hiromichi|last2=Aoki|first2=Kosuke|last3=Chiba|first3=Kenichi|last4=Sato|first4=Yusuke|last5=Shiozawa|first5=Yusuke|last6=Shiraishi|first6=Yuichi|last7=Shimamura|first7=Teppei|last8=Niida|first8=Atsushi|last9=Motomura|first9=Kazuya|date=2015-05|title=Mutational landscape and clonal architecture in grade II and III gliomas|url=https://pubmed.ncbi.nlm.nih.gov/25848751|journal=Nature Genetics|volume=47|issue=5|pages=458–468|doi=10.1038/ng.3273|issn=1546-1718|pmid=25848751}}</ref>
 |TSG
 |15%<ref name=":10" />
 |
 |N/A
@@ Line 261: / Line 387: @@
 |''PIK3CA'' <ref>{{Cite journal|last=Tateishi|first=Kensuke|last2=Nakamura|first2=Taishi|last3=Juratli|first3=Tareq A.|last4=Williams|first4=Erik A.|last5=Matsushita|first5=Yuko|last6=Miyake|first6=Shigeta|last7=Nishi|first7=Mayuko|last8=Miller|first8=Julie J.|last9=Tummala|first9=Shilpa S.|date=2019-07-15|title=PI3K/AKT/mTOR Pathway Alterations Promote Malignant Progression and Xenograft Formation in Oligodendroglial Tumors|url=https://pubmed.ncbi.nlm.nih.gov/30975663|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=25|issue=14|pages=4375–4387|doi=10.1158/1078-0432.CCR-18-4144|issn=1557-3265|pmc=6924174|pmid=30975663}}</ref> <ref>{{Cite journal|last=Broderick|first=Daniel K.|last2=Di|first2=Chunhui|last3=Parrett|first3=Timothy J.|last4=Samuels|first4=Yardena R.|last5=Cummins|first5=Jordan M.|last6=McLendon|first6=Roger E.|last7=Fults|first7=Daniel W.|last8=Velculescu|first8=Victor E.|last9=Bigner|first9=Darell D.|date=2004-08-01|title=Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas|url=https://pubmed.ncbi.nlm.nih.gov/15289301|journal=Cancer Research|volume=64|issue=15|pages=5048–5050|doi=10.1158/0008-5472.CAN-04-1170|issn=0008-5472|pmid=15289301}}</ref>
 |Oncogene
 |10%<ref name=":18">{{Cite journal|last=Brito|first=Cheila|last2=Tomás|first2=Ana|last3=Azevedo|first3=Ana|last4=Esteves|first4=Susana|last5=Mafra|first5=Manuela|last6=Roque|first6=Lúcia|last7=Pojo|first7=Marta|date=2022|title=PIK3CA Mutations in Diffuse Gliomas: An Update on Molecular Stratification, Prognosis, Recurrence, and Aggressiveness|url=https://pubmed.ncbi.nlm.nih.gov/35023985|journal=Clinical Medicine Insights. Oncology|volume=16|pages=11795549211068804|doi=10.1177/11795549211068804|issn=1179-5549|pmc=8743979|pmid=35023985}}</ref>
 |
 |N/A
@@ Line 276: / Line 402: @@
 |
 |No
 |Yes
 |No
 |Found recurrently in CNS WHO grade 3  tumors<ref name=":19" />
 |}
 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.
@@ Line 286: / Line 412: @@
 -         IDH-mutant, 1p/19q-codeleted oligodendrogliomas have hypermethylation of multiple CpG islands (PMID: 20399149)
-*   This corresponds to a distinct glioma CpG island methylator phenotype (G-CIMP)
+*  This corresponds to a distinct glioma CpG island methylator phenotype (G-CIMP)
-**   More prevalent in lower grade gliomas
+**  More prevalent in lower grade gliomas
-** Tightly associated with ''IDH1/2'' mutations
+**Tightly associated with ''IDH1/2'' mutations
 ==Genes and Main Pathways Involved==
+<br />
-Put your text here and fill in the table
 {| class="wikitable sortable"
 |-
@@ Line 307: / Line 432: @@
 |''CIC''; inactivating mutation
 |Histone deacetylation upregulates MAPK  signaling
 |Increased cell growth and proliferation<ref>{{Cite journal|last=Weissmann|first=Simon|last2=Cloos|first2=Paul A.|last3=Sidoli|first3=Simone|last4=Jensen|first4=Ole N.|last5=Pollard|first5=Steven|last6=Helin|first6=Kristian|date=2018-08-01|title=The Tumor Suppressor CIC Directly Regulates MAPK Pathway Genes via Histone Deacetylation|url=https://pubmed.ncbi.nlm.nih.gov/29844126|journal=Cancer Research|volume=78|issue=15|pages=4114–4125|doi=10.1158/0008-5472.CAN-18-0342|issn=1538-7445|pmc=6076439|pmid=29844126}}</ref>
 |-
 |''FUBP1''; activating mutation
 |FUBP1 deficiency alters cells cycle  progression, especially in S phase by downregulating cyclin A
 |Increased survival advantage to  metabolic stress and chemotherapeutic drugs<ref name=":15" />
 |-
 |''NOTCH1''; inactivating mutation
 |Affects epidermal growth factor-like  domain leading to protein loss of function
 |Induces accelerated cell proliferation<ref name=":17" />
 |}
 ==Genetic Diagnostic Testing Methods==
@@ Line 321: / Line 446: @@
 -         1p/19q co-deletion
-*   FISH
+*  FISH
-*   Multiplex PCR
+*  Multiplex PCR
-*   Chromosomal microarray
+*  Chromosomal microarray
-*   Next Generation Sequencing
+*  Next Generation Sequencing
 ==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>
+==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==
-Put your text placeholder here (use "Link" icon at top of page)
+''[https://ccga.io/index.php/IDH1 IDH1]''
+''[https://ccga.io/index.php/IDH2 IDH2]''
 ==References==
 <references />
-(use "Cite" icon at top of page)
+==Notes==
-===EXAMPLE Book===
-#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
-==Notes==
+<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
-<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
+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>.
+[[Category:CNS5]]
+[[Category:DISEASE]]
+[[Category:Diseases O]]

CNS5:Oligodendroglioma, IDH-mutant and 1p/19q-codeleted: Difference between revisions