@@ Line 1: / Line 1: @@
 ==Primary Author(s)*==
-Riley Lochner, MD, University Hospitals/Case Western Reserve University
+Riley Lochner MD, MS, Neuropathology Fellow Houston Methodist/Texas Children’s/MD Anderson Cancer Center
-Shashi Shetty, PhD, University Hospitals/Case Western Reserve University
+Shashirekha Shetty, PhD, Director, Cytogenetics Laboratory, Center for Human Genetics Laboratory, University Hospitals
 __TOC__
@@ Line 9: / Line 9: @@
 ==Cancer Category/Type==
-Put your text here
+Central nervous system – Diffuse gliomas
 ==Cancer Sub-Classification / Subtype==
-Put your text here
+Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
 ==Definition / Description of Disease==
-Put your text here
+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==
-Put your text here
+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==
-Put your text here
+-         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==
-Put your text here and fill in the table
+-         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'''
-|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+|Seizures<ref name=":4" />
-EXAMPLE B-symptoms (weight loss, fever, night sweats)
+Headache
-EXAMPLE Fatigue
+Signs  of increased intracranial pressure
-EXAMPLE Lymphadenopathy (uncommon)
+-           Focal neurologic deficits
+-           Cognitive changes
+Asymptomatic
+-           Increasingly an incidental finding  on neuroimaging (PMID: 29186201)
 |-
 |'''Laboratory Findings'''
-|EXAMPLE Cytopenias
+|Not  applicable
-EXAMPLE Lymphocytosis (low level)
 |}
 ==Sites of Involvement==
-Put your text here
+-         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==
-Put your text here
+-         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==
-Put your text here and fill in the table
+<br />
 {| class="wikitable sortable"
@@ Line 62: / Line 114: @@
 !Finding!!Marker
 |-
-|Positive (universal)||EXAMPLE CD1
+|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)||EXAMPLE CD2
+|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)||EXAMPLE CD3
+|Negative (universal)||Lack diffuse p53<ref name=":5" />
 |-
-|Negative (subset)||EXAMPLE CD4
+|Negative (subset)||N/A
 |}
 ==Chromosomal Rearrangements (Gene Fusions)==
-Put your text here and fill in the table
+-         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
 {| class="wikitable sortable"
@@ Line 83: / Line 139: @@
 !Notes
 |-
-|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+|t(1;19)(p10;q10)
-EXAMPLE 30% (add reference)
+|
+|der[t(1;19)(q10;p10)
+|100%
 |Yes
 |No
-|Yes
+|No
-|EXAMPLE
+|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>
-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).
 |}
@@ Line 105: / Line 161: @@
 !Notes
 |-
-|EXAMPLE
+|9
+|Loss
+|chr9:21082471-23839529 [hg38]
-|EXAMPLE Loss
+<br />
-|EXAMPLE
+|9p21.3
+|No
-chr7:1- 159,335,973 [hg38]
-|EXAMPLE
-chr7
-|Yes
 |Yes
 |No
-|EXAMPLE
+|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>
-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 reference).
-|-
-|EXAMPLE
-|EXAMPLE Gain
-|EXAMPLE
-chr8:1-145,138,636 [hg38]
-|EXAMPLE
-chr8
-|No
-|No
-|No
-|EXAMPLE
-Common recurrent secondary finding for t(8;21) (add reference).
 |}
 ==Characteristic Chromosomal Patterns==
@@ Line 151: / Line 183: @@
 !Notes
 |-
-|EXAMPLE
+|Co-deletion of  1p and 19q
-Co-deletion of 1p and 18q
 |Yes
 |No
 |No
-|EXAMPLE:
+|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>
-See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 |}
 ==Gene Mutations (SNV/INDEL)==
@@ Line 173: / Line 201: @@
 !Notes
 |-
-|EXAMPLE: TP53; Variable LOF mutations
+|''IDH1'' p.R132H <ref name=":8">{{Cite journal|last=Eckel-Passow|first=Jeanette E.|last2=Lachance|first2=Daniel H.|last3=Molinaro|first3=Annette M.|last4=Walsh|first4=Kyle M.|last5=Decker|first5=Paul A.|last6=Sicotte|first6=Hugues|last7=Pekmezci|first7=Melike|last8=Rice|first8=Terri|last9=Kosel|first9=Matt L.|date=2015-06-25|title=Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors|url=https://pubmed.ncbi.nlm.nih.gov/26061753|journal=The New England Journal of Medicine|volume=372|issue=26|pages=2499–2508|doi=10.1056/NEJMoa1407279|issn=1533-4406|pmc=4489704|pmid=26061753}}</ref>
+|Oncogene  (Intrinsically TSG, but is oncogenic in activity) <ref name=":9">{{Cite journal|last=Tiburcio|first=Patricia D. B.|last2=Xiao|first2=Bing|last3=Chai|first3=Yi|last4=Asper|first4=Sydney|last5=Tripp|first5=Sheryl R.|last6=Gillespie|first6=David L.|last7=Jensen|first7=Randy L.|last8=Huang|first8=L. Eric|date=2018-10-12|title=IDH1R132H is intrinsically tumor-suppressive but functionally attenuated by the glutamate-rich cerebral environment|url=https://pubmed.ncbi.nlm.nih.gov/30416682|journal=Oncotarget|volume=9|issue=80|pages=35100–35113|doi=10.18632/oncotarget.26203|issn=1949-2553|pmc=6205547|pmid=30416682}}</ref>
+|90%<ref>{{Cite journal|last=Hartmann|first=Christian|last2=Meyer|first2=Jochen|last3=Balss|first3=Jörg|last4=Capper|first4=David|last5=Mueller|first5=Wolf|last6=Christians|first6=Arne|last7=Felsberg|first7=Jörg|last8=Wolter|first8=Marietta|last9=Mawrin|first9=Christian|date=2009-10|title=Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas|url=https://pubmed.ncbi.nlm.nih.gov/19554337|journal=Acta Neuropathologica|volume=118|issue=4|pages=469–474|doi=10.1007/s00401-009-0561-9|issn=1432-0533|pmid=19554337}}</ref> <ref name=":10">{{Cite journal|last=Cancer Genome Atlas Research Network|last2=Brat|first2=Daniel J.|last3=Verhaak|first3=Roel G. W.|last4=Aldape|first4=Kenneth D.|last5=Yung|first5=W. K. Alfred|last6=Salama|first6=Sofie R.|last7=Cooper|first7=Lee A. D.|last8=Rheinbay|first8=Esther|last9=Miller|first9=C. Ryan|date=2015-06-25|title=Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26061751|journal=The New England Journal of Medicine|volume=372|issue=26|pages=2481–2498|doi=10.1056/NEJMoa1402121|issn=1533-4406|pmc=4530011|pmid=26061751}}</ref>
+|
+|N/A
+|Yes
+|Yes
+|No
+|''IDH1'' codon 132 mutation required for diagnosis; other most frequent mutation  hotspot is ''IDH2'' codon 172
+|-
+|''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
+|Yes
+|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''
+|TSG
+|24% CNS WHO grade 2;
-EXAMPLE:
+% CNS WHO grade 3
-EGFR; Exon 20 mutations
+% <ref name=":10" /> <ref name=":8" />
+|
+|N/A
+|No
+|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>
+|Both TSG and oncogene <ref>{{Cite journal|last=Kang|first=Mingyu|last2=Kim|first2=Hyeon Ji|last3=Kim|first3=Tae-Jun|last4=Byun|first4=Jin-Seok|last5=Lee|first5=Jae-Ho|last6=Lee|first6=Deok Heon|last7=Kim|first7=Wanil|last8=Kim|first8=Do-Yeon|date=2020-05-28|title=Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival|url=https://pubmed.ncbi.nlm.nih.gov/32481602|journal=Cells|volume=9|issue=6|pages=1347|doi=10.3390/cells9061347|issn=2073-4409|pmc=7349734|pmid=32481602}}</ref>
+|16% CNS WHO grade 2
-EXAMPLE: BRAF; Activating mutations
+% grade 3
-|EXAMPLE: TSG
-|EXAMPLE: 20% (COSMIC)
-EXAMPLE: 30% (add Reference)
+-30%<ref name=":16" />
-|EXAMPLE: IDH1 R123H
+|
-|EXAMPLE: EGFR amplification
+|N/A
+|No
+|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
+|No
+|Yes
+|No
+|Shorter survival and worse histology <ref name=":17">{{Cite journal|last=Aoki|first=Kosuke|last2=Nakamura|first2=Hideo|last3=Suzuki|first3=Hiromichi|last4=Matsuo|first4=Keitaro|last5=Kataoka|first5=Keisuke|last6=Shimamura|first6=Teppei|last7=Motomura|first7=Kazuya|last8=Ohka|first8=Fumiharu|last9=Shiina|first9=Satoshi|date=2018-01-10|title=Prognostic relevance of genetic alterations in diffuse lower-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/29016839|journal=Neuro-Oncology|volume=20|issue=1|pages=66–77|doi=10.1093/neuonc/nox132|issn=1523-5866|pmc=5761527|pmid=29016839}}</ref> <ref>{{Cite journal|last=Halani|first=Sameer H.|last2=Yousefi|first2=Safoora|last3=Velazquez Vega|first3=Jose|last4=Rossi|first4=Michael R.|last5=Zhao|first5=Zheng|last6=Amrollahi|first6=Fatemeh|last7=Holder|first7=Chad A.|last8=Baxter-Stoltzfus|first8=Amelia|last9=Eschbacher|first9=Jennifer|date=2018|title=Multi-faceted computational assessment of risk and progression in oligodendroglioma implicates NOTCH and PI3K pathways|url=https://pubmed.ncbi.nlm.nih.gov/30417117|journal=NPJ precision oncology|volume=2|pages=24|doi=10.1038/s41698-018-0067-9|issn=2397-768X|pmc=6219505|pmid=30417117}}</ref>
+|-
+|''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
+|No
+|No
+|Possibly in future<ref name=":18" />
 |
-|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+|-
+|''TCF12''
+|TSG
+|7.5% of CNS WHO grade 3<ref name=":19">{{Cite journal|last=Labreche|first=Karim|last2=Simeonova|first2=Iva|last3=Kamoun|first3=Aurélie|last4=Gleize|first4=Vincent|last5=Chubb|first5=Daniel|last6=Letouzé|first6=Eric|last7=Riazalhosseini|first7=Yasser|last8=Dobbins|first8=Sara E.|last9=Elarouci|first9=Nabila|date=2015-06-12|title=TCF12 is mutated in anaplastic oligodendroglioma|url=https://pubmed.ncbi.nlm.nih.gov/26068201|journal=Nature Communications|volume=6|pages=7207|doi=10.1038/ncomms8207|issn=2041-1723|pmc=4490400|pmid=26068201}}</ref>
 <br />
+|
+|
+|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 196: / Line 284: @@
 ==Epigenomic Alterations==
-Put your text here
+-         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)
+**   More prevalent in lower grade gliomas
+** Tightly associated with ''IDH1/2'' mutations
 ==Genes and Main Pathways Involved==
@@ Line 205: / Line 297: @@
 !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 |-
-|EXAMPLE: BRAF and MAP2K1; Activating mutations
+|''IDH1/2''; activating  mutation
-|EXAMPLE: MAPK signaling
+|Pathologic  upregulation of 2-hydroxyglutarate leading to increased MAPK signaling
-|EXAMPLE: Increased cell growth and proliferation
+|Increased  cell growth and proliferation<ref name=":9" />
+|-
+|''TERT'' promoter; activating mutation
+|Generates de novo ETS transcription  factor binding sites upregulating expression
+|Telomere stabilization, cell  proliferation and immortalization<ref name=":11" /><ref name=":12" /> <ref name=":13" />
+|-
+|''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>
 |-
-|EXAMPLE: CDKN2A; Inactivating mutations
+|''FUBP1''; activating mutation
-|EXAMPLE: Cell cycle regulation
+|FUBP1 deficiency alters cells cycle  progression, especially in S phase by downregulating cyclin A
-|EXAMPLE: Unregulated cell division
+|Increased survival advantage to  metabolic stress and chemotherapeutic drugs<ref name=":15" />
 |-
-|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+|''NOTCH1''; inactivating mutation
-|EXAMPLE:  Histone modification, chromatin remodeling
+|Affects epidermal growth factor-like  domain leading to protein loss of function
-|EXAMPLE:  Abnormal gene expression program
+|Induces accelerated cell proliferation<ref name=":17" />
 |}
 ==Genetic Diagnostic Testing Methods==
-Put your text here
+-         1p/19q co-deletion
+*   FISH
+*   Multiplex PCR
+*   Chromosomal microarray
+*   Next Generation Sequencing
 ==Familial Forms==
-Put your text here
+-         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==
-Put your text here
 ==Links==

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