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

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 -         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
+*  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" />)
+*  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 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 (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" />)
+**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 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" />
+*  CNS WHO grade 3 oligodendrogliomas account of primary brain tumors in the US(PMID: 34608945)<ref name=":1" />
 ==Clinical Features==
@@ Line 53: / Line 53: @@
 -         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>
+*  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>
@@ Line 82: / Line 82: @@
 -         Approximately 60% of oligodendrogliomas occur within the frontal lobes with<ref name=":0" /><ref name=":1" />
-*   14-16% in the temporal lobe
+*  14-16% in the temporal lobe
-*   10-15% in the parietal lobe
+*  10-15% in the parietal lobe
-*   1-6% in the occipital lobe
+*  1-6% in the occipital lobe
-*   Less commonly basal ganglia / cerebellum brainstem
+*  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>
@@ Line 120: / Line 120: @@
 Synaptophysin (cytoplasmic dot-like pattern<ref>{{Cite journal|last=Perry|first=Arie|last2=Burton|first2=Stephanie S.|last3=Fuller|first3=Gregory N.|last4=Robinson|first4=Christopher A.|last5=Palmer|first5=Cheryl A.|last6=Resch|first6=Lothar|last7=Bigio|first7=Eileen H.|last8=Gujrati|first8=Meena|last9=Rosenblum|first9=Marc K.|date=2010-08|title=Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall|url=https://pubmed.ncbi.nlm.nih.gov/20464403|journal=Acta Neuropathologica|volume=120|issue=2|pages=237–252|doi=10.1007/s00401-010-0695-9|issn=1432-0533|pmc=2892612|pmid=20464403}}</ref>)
 |-
 |Negative (universal)||Lack diffuse p53<ref name=":5" />
 |-
 |Negative (subset)||N/A
@@ Line 129: / Line 129: @@
 -         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 213: / Line 213: @@
 |''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 219: @@
 |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 233: @@
 |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 241: @@
 % grade 3
 -30%<ref name=":16" />
 |
 |N/A
@@ Line 247: / Line 247: @@
 |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 261: @@
 |''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 276: @@
 |
 |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 286: @@
 -         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==
@@ Line 307: / Line 307: @@
 |''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 321: @@
 -         1p/19q co-deletion
-*   FISH
+*  FISH
-*   Multiplex PCR
+*  Multiplex PCR
-*   Chromosomal microarray
+*  Chromosomal microarray
-*   Next Generation Sequencing
+*  Next Generation Sequencing
 ==Familial Forms==
@@ Line 332: / Line 332: @@
 ==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)
-===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==
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