Compendium of Cancer Genome Aberrations

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==Primary Author(s)*==
{{DISPLAYTITLE:Diffuse astrocytoma, MYB- or MYBL1-altered}}


Put your text here
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]


__TOC__
{{Under Construction}}


==Cancer Category/Type==
<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)*==


Put your text here
Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University


==Cancer Sub-Classification / Subtype==
==WHO Classification of Disease==


Put your text here
{| class="wikitable"
 
!Structure
==Definition / Description of Disease==
!Disease
 
|-
Put your text here
|Book
 
|Central Nervous System Tumours (5th ed.)
==Synonyms / Terminology==
|-
 
|Category
Put your text here
|Gliomas, glioneuronal tumours, and neuronal tumours
 
|-
==Epidemiology / Prevalence==
|Family
 
|Gliomas, glioneuronal tumours, and neuronal tumours
Put your text here
|-
|Type
|Paediatric-type diffuse low-grade gliomas
|-
|Subtype(s)
|Diffuse astrocytoma, MYB- or MYBL1-altered
|}


==Clinical Features==
==Related Terminology==


Put your text here and fill in the table
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|N/A
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|EXAMPLE Cytopenias
|Isomorphic astrocytoma variant; isomorphic diffuse glioma
 
EXAMPLE Lymphocytosis (low level)
|}
|}


==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>
{| class="wikitable sortable"
|-
!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
|-
|<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).
|-
|<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>


Put your text here
''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).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''


==Morphologic Features==


Put your text here
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>


==Immunophenotype==
Both balanced and unbalanced forms are observed by FISH (add references).
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|<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
|
|
|-
|-
|Positive (universal)||EXAMPLE CD1
|
|-
|
|Positive (subset)||EXAMPLE CD2
|
|-
|
|Negative (universal)||EXAMPLE CD3
|
|-
|
|Negative (subset)||EXAMPLE CD4
|
|
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==


Put your text here and fill in the table


'''Add content below into table above''' -      
''MYB'' or ''MYBL1'' rearrangement
''MYB'' or ''MYBL1'' amplification
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 81: Line 118:
!Notes
!Notes
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|6q23.3 rearrangement
EXAMPLE 30% (add reference)
|
|
|
|Yes
|Yes
|
|Multiple potential  partners
|-
|8q13.1 rearrangement
|
|
|
|Yes
|Yes
|
|Multiple potential  partners
|-
|del(6)(q23.3q26); t(6;6)(q23.3;q26)
|''MYB::QKI''
|
|
|Yes
|Yes
|No
|Yes
|Yes
|EXAMPLE
|
|Creates fusion oncogenic protein
|}
 


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).
|}
==Individual Region Genomic Gain/Loss/LOH==
==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>
7
|<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>
8
|<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>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; 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.
|-
|
|
|
|
|
|
|
|}


Put your text here and fill in the table
 
'''Add content below into table above''' -      
''MYB'' or ''MYBL1'' copy number variation as identified by chromosomal microarray or FISH


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 103: Line 214:
!Notes
!Notes
|-
|-
|EXAMPLE
|6
 
|Amp/Loss/Gain
7
|135502446-135540310 [GRCh37]
|EXAMPLE Loss
|6q23.3
|EXAMPLE
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
 
chr7
|Yes
|Yes
|Yes
|Yes
|No
|Yes<ref>{{Cite journal|last=Trkova|first=Katerina|last2=Sumerauer|first2=David|last3=Krskova|first3=Lenka|last4=Vicha|first4=Ales|last5=Koblizek|first5=Miroslav|last6=Votava|first6=Tomas|last7=Priban|first7=Vladimir|last8=Zapotocky|first8=Michal|date=2023-09|title=DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy|url=https://pubmed.ncbi.nlm.nih.gov/37165121|journal=Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery|volume=39|issue=9|pages=2509–2513|doi=10.1007/s00381-023-05976-3|issn=1433-0350|pmc=PMC10432314|pmid=37165121}}</ref>
|EXAMPLE
|<ref>{{Cite journal|last=Ramkissoon|first=Lori A.|last2=Horowitz|first2=Peleg M.|last3=Craig|first3=Justin M.|last4=Ramkissoon|first4=Shakti H.|last5=Rich|first5=Benjamin E.|last6=Schumacher|first6=Steven E.|last7=McKenna|first7=Aaron|last8=Lawrence|first8=Michael S.|last9=Bergthold|first9=Guillaume|date=2013-05-14|title=Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1|url=https://pubmed.ncbi.nlm.nih.gov/23633565|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=20|pages=8188–8193|doi=10.1073/pnas.1300252110|issn=1091-6490|pmc=3657784|pmid=23633565}}</ref><ref>{{Cite journal|last=Bale|first=Tejus A.|last2=Rosenblum|first2=Marc K.|date=2022-07|title=The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors|url=https://pubmed.ncbi.nlm.nih.gov/35218102|journal=Brain Pathology (Zurich, Switzerland)|volume=32|issue=4|pages=e13060|doi=10.1111/bpa.13060|issn=1750-3639|pmc=9245930|pmid=35218102}}</ref><ref>{{Cite journal|last=Trkova|first=Katerina|last2=Sumerauer|first2=David|last3=Krskova|first3=Lenka|last4=Vicha|first4=Ales|last5=Koblizek|first5=Miroslav|last6=Votava|first6=Tomas|last7=Priban|first7=Vladimir|last8=Zapotocky|first8=Michal|date=2023-09|title=DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy|url=https://pubmed.ncbi.nlm.nih.gov/37165121|journal=Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery|volume=39|issue=9|pages=2509–2513|doi=10.1007/s00381-023-05976-3|issn=1433-0350|pmc=PMC10432314|pmid=37165121}}</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
|8
 
|Amp/Loss/Gain
8
|67474410-67525453 [GRCh37]
|EXAMPLE Gain
|8q13.1
|EXAMPLE
|Yes
 
|Yes
chr8:1-145,138,636 [hg38]
|Unknown
|EXAMPLE
|<ref>{{Cite journal|last=Ramkissoon|first=Lori A.|last2=Horowitz|first2=Peleg M.|last3=Craig|first3=Justin M.|last4=Ramkissoon|first4=Shakti H.|last5=Rich|first5=Benjamin E.|last6=Schumacher|first6=Steven E.|last7=McKenna|first7=Aaron|last8=Lawrence|first8=Michael S.|last9=Bergthold|first9=Guillaume|date=2013-05-14|title=Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1|url=https://pubmed.ncbi.nlm.nih.gov/23633565|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=20|pages=8188–8193|doi=10.1073/pnas.1300252110|issn=1091-6490|pmc=3657784|pmid=23633565}}</ref><ref>{{Cite journal|last=Bale|first=Tejus A.|last2=Rosenblum|first2=Marc K.|date=2022-07|title=The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors|url=https://pubmed.ncbi.nlm.nih.gov/35218102|journal=Brain Pathology (Zurich, Switzerland)|volume=32|issue=4|pages=e13060|doi=10.1111/bpa.13060|issn=1750-3639|pmc=9245930|pmid=35218102}}</ref>
 
chr8
|No
|No
|No
|EXAMPLE
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
|}
==Characteristic Chromosomal Patterns==


Put your text here


==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"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!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
|
|
|-
|-
|EXAMPLE
|
|
|
|
|
|
|}


Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:


See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
==Gene Mutations (SNV/INDEL)==


Put your text here and fill in the table
'''Add content below into table above''' -      
Possible detection of double minutes or homogeneously stained regions by G-banding for amplification; will require confirmation of being associated with MYB or MYBL (likely by chromosomal microarray)


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Chromosomal Pattern
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
!Notes
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|6q23.3 hsr; '' MYB'' amplification <span lang="EN-US">Scott C. Smith,


EXAMPLE:
PhD, FACMG; SUNY Upstate Medical University
|No
|Unknown
|Unknown
|
|-
|8q13.1 hsr; ''MYBL1'' amplification<span lang="EN-US">Scott C. Smith,


EGFR; Exon 20 mutations
PhD, FACMG; SUNY Upstate Medical University
 
|No
EXAMPLE: BRAF; Activating mutations
|Unknown
|EXAMPLE: TSG
|Unknown
|EXAMPLE: 20% (COSMIC)
 
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


==Epigenomic Alterations==
Put your text here


==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|''MYB/MYBL1'' 3’-deletion
|EXAMPLE: MAPK signaling
|MYB/MYBL1 protooncogene
|EXAMPLE: Increased cell growth and proliferation
|Deregulation  of MYB/MYBL1
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|''MYB/MYBL1'' amplification
|EXAMPLE: Cell cycle regulation
|MYB/MYBL1 protooncogene
|EXAMPLE: Unregulated cell division
|Overexpression of MYB/MYBL1
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Put your text here
Sequencing, PCR, RT-PCR, chromosomal microarray, FISH, possibly detection of double minutes or homogenously stained regions by G-banding


==Familial Forms==
==Familial Forms==
N/A
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:


Put your text here
* Diffuse astrocytoma, ''MYB'' or ''MYBL1''-altered is one of several newly recognized tumor types in the 5<sup>th</sup> edition of the ''WHO Classification of Tumors of the Central Nervous System''. The newly recognized classifications were in response to advances in understanding of pediatric-type gliomas, facilitated by an increased molecular characterization of these tumors. Diffuse astrocytoma, MYB or MYBL1-altered is a subset of diffuse low-grade glioma with amplifications, structural variants, and fusions involving the ''MYB'' and ''MYBL1'' protooncogenes. Diffuse astrocytoma, MYB or MYBL1-altered subtypes are without characteristic histological features of angiocentric glioma<ref>{{Cite journal|last=Slegers|first=Rutger Juriaan|last2=Blumcke|first2=Ingmar|date=2020-03-09|title=Low-grade developmental and epilepsy associated brain tumors: a critical update 2020|url=https://pubmed.ncbi.nlm.nih.gov/32151273|journal=Acta Neuropathologica Communications|volume=8|issue=1|pages=27|doi=10.1186/s40478-020-00904-x|issn=2051-5960|pmc=7063704|pmid=32151273}}</ref><ref>{{Cite journal|last=Bandopadhayay|first=Pratiti|last2=Ramkissoon|first2=Lori A.|last3=Jain|first3=Payal|last4=Bergthold|first4=Guillaume|last5=Wala|first5=Jeremiah|last6=Zeid|first6=Rhamy|last7=Schumacher|first7=Steven E.|last8=Urbanski|first8=Laura|last9=O'Rourke|first9=Ryan|date=2016-03|title=MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism|url=https://pubmed.ncbi.nlm.nih.gov/26829751|journal=Nature Genetics|volume=48|issue=3|pages=273–282|doi=10.1038/ng.3500|issn=1546-1718|pmc=4767685|pmid=26829751}}</ref>. A related group of diffuse gliomas, the isomorphic glioma, occur predominantly in adults and are typically well-differentiated, low to moderately cellular, comprised of astrocytes with rounded nuclei and regular chromatin structures, and have low proliferative indices<ref>{{Cite journal|last=Wefers|first=Annika K.|last2=Stichel|first2=Damian|last3=Schrimpf|first3=Daniel|last4=Coras|first4=Roland|last5=Pages|first5=Mélanie|last6=Tauziède-Espariat|first6=Arnault|last7=Varlet|first7=Pascale|last8=Schwarz|first8=Daniel|last9=Söylemezoglu|first9=Figen|date=2020-01|title=Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course|url=https://pubmed.ncbi.nlm.nih.gov/31563982|journal=Acta Neuropathologica|volume=139|issue=1|pages=193–209|doi=10.1007/s00401-019-02078-w|issn=1432-0533|pmc=7477753|pmid=31563982}}</ref><ref>{{Cite journal|last=Chiang|first=Jason|last2=Harreld|first2=Julie H.|last3=Tinkle|first3=Christopher L.|last4=Moreira|first4=Daniel C.|last5=Li|first5=Xiaoyu|last6=Acharya|first6=Sahaja|last7=Qaddoumi|first7=Ibrahim|last8=Ellison|first8=David W.|date=2019-12|title=A single-center study of the clinicopathologic correlates of gliomas with a MYB or MYBL1 alteration|url=https://pubmed.ncbi.nlm.nih.gov/31595312|journal=Acta Neuropathologica|volume=138|issue=6|pages=1091–1092|doi=10.1007/s00401-019-02081-1|issn=1432-0533|pmc=7467132|pmid=31595312}}</ref>. These adult diffuse gliomas exhibit alterations of ''MYBL1'' rather than ''MYB''. Gene fusions with multiple partners characterize the pediatric ''MYB'' or ''MYBL1-''altered gliomas<ref>{{Cite journal|last=Ramkissoon|first=Lori A.|last2=Horowitz|first2=Peleg M.|last3=Craig|first3=Justin M.|last4=Ramkissoon|first4=Shakti H.|last5=Rich|first5=Benjamin E.|last6=Schumacher|first6=Steven E.|last7=McKenna|first7=Aaron|last8=Lawrence|first8=Michael S.|last9=Bergthold|first9=Guillaume|date=2013-05-14|title=Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1|url=https://pubmed.ncbi.nlm.nih.gov/23633565|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=20|pages=8188–8193|doi=10.1073/pnas.1300252110|issn=1091-6490|pmc=3657784|pmid=23633565}}</ref><ref>{{Cite journal|last=Barinfeld|first=Orit|last2=Zahavi|first2=Alon|last3=Weiss|first3=Shirel|last4=Toledano|first4=Helen|last5=Michowiz|first5=Shalom|last6=Goldenberg-Cohen|first6=Nitza|date=2022|title=Genetic Alteration Analysis of IDH1, IDH2, CDKN2A, MYB and MYBL1 in Pediatric Low-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/35574540|journal=Frontiers in Surgery|volume=9|pages=880048|doi=10.3389/fsurg.2022.880048|issn=2296-875X|pmc=9096721|pmid=35574540}}</ref>. The most frequently identified fusion is with ''QKI''<ref>{{Cite journal|last=Suh|first=Ye Yoon|last2=Lee|first2=Kwanghoon|last3=Shim|first3=Yu-Mi|last4=Phi|first4=Ji Hoon|last5=Park|first5=Chul-Kee|last6=Kim|first6=Seung-Ki|last7=Choi|first7=Seung Hong|last8=Yun|first8=Hongseok|last9=Park|first9=Sung-Hye|date=2023-02-21|title=MYB/MYBL1::QKI fusion-positive diffuse glioma|url=https://pubmed.ncbi.nlm.nih.gov/36592415|journal=Journal of Neuropathology and Experimental Neurology|volume=82|issue=3|pages=250–260|doi=10.1093/jnen/nlac123|issn=1554-6578|pmc=9941827|pmid=36592415}}</ref><ref>{{Cite journal|last=Jain|first=Payal|last2=Resnick|first2=Adam C.|date=2017-03-04|title=MYB-QKI drives childhood brain tumors via tripartite mechanism|url=https://pubmed.ncbi.nlm.nih.gov/27973981|journal=Cell Cycle (Georgetown, Tex.)|volume=16|issue=5|pages=390–391|doi=10.1080/15384101.2016.1260990|issn=1551-4005|pmc=5351923|pmid=27973981}}</ref>''.'' The ''MYB'' or ''MYBL1-''altered diffuse gliomas in both children and adults are generally indolent and behave in a WHO grade 1 fashion.


==Additional Information==
The <u>clinical features</u> of this disease are detailed below:
 
* Medically refractory epilepsy since childhood.
* Signs and symptoms - History of epilepsy or seizure; Magnetic resonance imaging (MRI): well-delineated, occasionally infiltrative-appearing, non-enhancing T1-hypointense, T2-fluid attenuated inversion recovery-hyperintense lesion without restricted diffusion<ref>{{Cite journal|last=Fabbri|first=Viscardo Paolo|last2=Caporalini|first2=Chiara|last3=Asioli|first3=Sofia|last4=Buccoliero|first4=Annamaria|date=2022-12|title=Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome|url=https://pubmed.ncbi.nlm.nih.gov/36534420|journal=Pathologica|volume=114|issue=6|pages=410–421|doi=10.32074/1591-951X-828|issn=1591-951X|pmc=9763978|pmid=36534420}}</ref>
* Laboratory findings - Genetics: Negative for ''IDH1'' p.R132H, ''BRAF'' p.V600E; positive for ''MYBL1'' or ''MYB'' rearrangement, amplification, or copy number change
 
The <u>sites of involvement</u> of this disease are detailed below:
 
* Supratentorial (adult), cortical and subcortical regions of the cerebral cortex (pediatric)<ref>{{Cite journal|last=Fabbri|first=Viscardo Paolo|last2=Caporalini|first2=Chiara|last3=Asioli|first3=Sofia|last4=Buccoliero|first4=Annamaria|date=2022-12|title=Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome|url=https://pubmed.ncbi.nlm.nih.gov/36534420|journal=Pathologica|volume=114|issue=6|pages=410–421|doi=10.32074/1591-951X-828|issn=1591-951X|pmc=9763978|pmid=36534420}}</ref>
 
The <u>morphologic features</u> of this disease are detailed below:
 
* Histomorphology: minimally to moderately hypercellular tumor; diffuse infiltration by monomorphic cells with ovoid to elongated nuclei, scant cytoplasm, fibrillary background<ref>{{Cite journal|last=Fabbri|first=Viscardo Paolo|last2=Caporalini|first2=Chiara|last3=Asioli|first3=Sofia|last4=Buccoliero|first4=Annamaria|date=2022-12|title=Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome|url=https://pubmed.ncbi.nlm.nih.gov/36534420|journal=Pathologica|volume=114|issue=6|pages=410–421|doi=10.32074/1591-951X-828|issn=1591-951X|pmc=9763978|pmid=36534420}}</ref><ref>{{Cite journal|last=Suh|first=Ye Yoon|last2=Lee|first2=Kwanghoon|last3=Shim|first3=Yu-Mi|last4=Phi|first4=Ji Hoon|last5=Park|first5=Chul-Kee|last6=Kim|first6=Seung-Ki|last7=Choi|first7=Seung Hong|last8=Yun|first8=Hongseok|last9=Park|first9=Sung-Hye|date=2023-02-21|title=MYB/MYBL1::QKI fusion-positive diffuse glioma|url=https://pubmed.ncbi.nlm.nih.gov/36592415|journal=Journal of Neuropathology and Experimental Neurology|volume=82|issue=3|pages=250–260|doi=10.1093/jnen/nlac123|issn=1554-6578|pmc=9941827|pmid=36592415}}</ref>
 
The <u>immunophenotype</u> of this disease is detailed below:
 
* Positivity for GFAP, below 1% Ki-67 index, negative for OLIG2 and IDH1 R132H<ref>{{Cite journal|last=Wefers|first=Annika K.|last2=Stichel|first2=Damian|last3=Schrimpf|first3=Daniel|last4=Coras|first4=Roland|last5=Pages|first5=Mélanie|last6=Tauziède-Espariat|first6=Arnault|last7=Varlet|first7=Pascale|last8=Schwarz|first8=Daniel|last9=Söylemezoglu|first9=Figen|date=2020-01|title=Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course|url=https://pubmed.ncbi.nlm.nih.gov/31563982|journal=Acta Neuropathologica|volume=139|issue=1|pages=193–209|doi=10.1007/s00401-019-02078-w|issn=1432-0533|pmc=7477753|pmid=31563982}}</ref>


Put your text here
* Positive (universal) - GFAP
* Positive (subset) - Ki-67 index below 1%
* Negative (universal) - OLIG2, IDH1 R132H


==Links==
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==References==
==References==
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==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.
<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.  


==Notes==
Prior Author(s):
<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.
<nowiki>*</nowiki>''Citation of this Page'': “Diffuse astrocytoma, MYB- or MYBL1-altered”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Diffuse astrocytoma, MYB- or MYBL1-altered</nowiki>.
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases D]]
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