Compendium of Cancer Genome Aberrations

CNS5:Diffuse astrocytoma, MYB- or MYBL1-altered: Difference between revisions

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{{DISPLAYTITLE:Diffuse astrocytoma, MYB- or MYBL1-altered}}
{{DISPLAYTITLE:Diffuse astrocytoma, MYB- or MYBL1-altered}}


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


{{Under Construction}}
{{Under Construction}}
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Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University
Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University


==WHO Classification of Disease==
==WHO Classification of Disease==
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|}
|}


==Definition / Description of Disease==
==Related Terminology==
 
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 paediatric-type gliomas, facilitated by an increased molecular characterisation of these tumours. 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.
 
==Clinical Features==


Medically refractory epilepsy since childhood.
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|History of epilepsy or seizure
|Acceptable
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>
|N/A
|-
|'''Laboratory Findings'''
|Genetics: Negative for ''IDH1'' p.R132H, ''BRAF'' p.V600E; positive for ''MYBL1'' or ''MYB'' rearrangement, amplification, or copy number change
|}
 
==Sites of Involvement==
 
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>
 
==Morphologic Features==
 
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>
 
==Immunophenotype==
 
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>
 
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||GFAP<span lang="EN-US">Scott C. Smith,
 
PhD, FACMG; SUNY Upstate Medical University
|-
|Positive (subset)||Ki-67 index below 1%
|-
|-
|Negative (universal)||OLIG2, IDH1 R132H
|Not Recommended
|Isomorphic astrocytoma variant; isomorphic diffuse glioma
|}
|}


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'''Add content below into table above''' -      
''MYB'' or ''MYBL1'' rearrangement
''MYB'' or ''MYBL1'' rearrangement


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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'''Add content below into table above''' -      
''MYB'' or ''MYBL1'' copy number variation as identified by chromosomal microarray or FISH
''MYB'' or ''MYBL1'' copy number variation as identified by chromosomal microarray or FISH


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!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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'''Add content below into table above''' -      
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)
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)


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|}
|}


==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.
==Epigenomic Alterations==
Put your text here
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


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Sequencing, PCR, RT-PCR, chromosomal microarray, FISH, possibly detection of double minutes or homogenously stained regions by G-banding
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
N/A


== Additional Information ==
==Additional Information==
This disease is defined/characterized as detailed below:
This disease is <u>defined/characterized</u> as detailed below:
 
 
The epidemiology/prevalence of this disease is detailed below:
 
 
The clinical features of this disease are detailed below:
 
Signs and symptoms -
 
Laboratory findings -


The sites of involvement of this disease are detailed below:
* 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.


The <u>clinical features</u> of this disease are detailed below:


The morphologic features 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:


The immunophenotype of this disease is 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>


Positive (universal) -
The <u>morphologic features</u> of this disease are detailed below:


Positive (majority) -
* 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>


Positive (subset) -
The <u>immunophenotype</u> of this disease is detailed below:


Negative (universal) -
* 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>


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


== Links ==
==Links==
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==References==
==References==
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