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

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{{DISPLAYTITLE:Diffuse astrocytoma, MYB- or MYBL1-altered}}
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[[CNS5:Table_of_Contents|Central Nervous System Tumours(WHO Classification, 5th ed.)]]
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{{Under Construction}}
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<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)*==
 
==Primary Author(s)*==
  
 
Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University
 
Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University
  
−
__TOC__
 
  
−
==Cancer Category/Type==
 
  
−
WHO Classification of Tumours of the Central Nervous System (5th Edition)
+
==WHO Classification of Disease==
  
−
==Cancer Sub-Classification / Subtype==
+
{| class="wikitable"
−
 
+
!Structure
−
Diffuse Astrocytoma, MYB- or MYBL1-Altered
+
!Disease
 +
|-
 +
|Book
 +
|Central Nervous System Tumours (5th ed.)
 +
|-
 +
|Category
 +
|Gliomas, glioneuronal tumours, and neuronal tumours
 +
|-
 +
|Family
 +
|Gliomas, glioneuronal tumours, and neuronal tumours
 +
|-
 +
|Type
 +
|Paediatric-type diffuse low-grade gliomas
 +
|-
 +
|Subtype(s)
 +
|Diffuse astrocytoma, MYB- or MYBL1-altered
 +
|}
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
Line 53: Line 73:
 
|}
 
|}
  
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==Chromosomal Rearrangements (Gene Fusions)==
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==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>
 +
 
 +
''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''
 +
 
 +
 
 +
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
 +
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
 +
|<span class="blue-text">EXAMPLE:</span> N/A
 +
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
 +
|<span class="blue-text">EXAMPLE:</span> T
 +
|
 +
|<span class="blue-text">EXAMPLE:</span>
 +
 
 +
Both balanced and unbalanced forms are observed by FISH (add references).
 +
|-
 +
|<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
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|}
 +
 
 +
 
 +
 
  
 
''MYB'' or ''MYBL1'' rearrangement
 
''MYB'' or ''MYBL1'' rearrangement
Line 94: Line 176:
 
|}
 
|}
 
 
 +
 +
 
==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.
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|}
 +
 +
 +
  
 
''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
Line 124: Line 263:
 
|<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=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>
 
|}
 
|}
−
==Characteristic Chromosomal Patterns==
+
 
 +
 
 +
==Characteristic Chromosomal or Other Global Mutational Patterns==
 +
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 +
{| class="wikitable sortable"
 +
|-
 +
!Chromosomal Pattern
 +
!Molecular Pathogenesis
 +
!'''Prevalence -'''
 +
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
 +
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
 +
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
 +
!'''Clinical Relevance Details/Other Notes'''
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span>
 +
Co-deletion of 1p and 18q
 +
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 +
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
 +
|<span class="blue-text">EXAMPLE:</span> D, P
 +
|
 +
|
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span>
 +
Microsatellite instability - hypermutated
 +
|
 +
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
 +
|<span class="blue-text">EXAMPLE:</span> P, T
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|}
 +
 
 +
 
 +
 
  
 
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)
Line 150: Line 328:
 
|
 
|
 
|}
 
|}
 +
 +
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
 +
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
 +
{| class="wikitable sortable"
 +
|-
 +
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
 +
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
 +
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
 +
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 +
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
 +
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
 +
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 +
|-
 +
|
 +
|
 +
|
 +
|}
 +
 +
 +
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
Line 163: Line 367:
 
|Overexpression  of MYB/MYBL1
 
|Overexpression  of MYB/MYBL1
 
|}
 
|}
 +
 +
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
  
Line 170: Line 376:
 
<references />
 
<references />
 
==Notes==
 
==Notes==
−
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
+
 
 +
 
 +
<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.
 +
 
 +
Prior Author(s):
 +
<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]]

Revision as of 12:51, 24 March 2025

Central Nervous System Tumours(WHO Classification, 5th ed.)

(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 HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Scott C. Smith, PhD, FACMG; SUNY Upstate Medical University


WHO Classification of Disease

Structure Disease
Book Central Nervous System Tumours (5th ed.)
Category Gliomas, glioneuronal tumours, and neuronal tumours
Family Gliomas, glioneuronal tumours, and neuronal tumours
Type Paediatric-type diffuse low-grade gliomas
Subtype(s) Diffuse astrocytoma, MYB- or MYBL1-altered

Definition / Description of Disease

Diffuse astrocytoma, MYB or MYBL1-altered is one of several newly recognized tumor types in the 5th 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[1][2]. 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[3][4]. These adult diffuse gliomas exhibit alterations of MYBL1 rather than MYB . Gene fusions with multiple partners characterize the pediatric MYB or MYBL1-altered gliomas[5][6]. The most frequently identified fusion is with QKI[7][8]. 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.

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[9]

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)[10]

Morphologic Features

Histomorphology: minimally to moderately hypercellular tumor; diffuse infiltration by monomorphic cells with ovoid to elongated nuclei, scant cytoplasm, fibrillary background[11][12]

Immunophenotype

Positivity for GFAP, below 1% Ki-67 index, negative for OLIG2 and IDH1 R132H[13]

Finding Marker
Positive (universal) GFAPScott C. Smith,

PhD, FACMG; SUNY Upstate Medical University

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

Gene Rearrangements

Put your text here and fill in the table (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.)

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
EXAMPLE: ABL1 EXAMPLE: BCR::ABL1 EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: Common (CML) EXAMPLE: D, P, T EXAMPLE: Yes (WHO, NCCN) EXAMPLE:

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).

EXAMPLE: CIC EXAMPLE: CIC::DUX4 EXAMPLE: 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. EXAMPLE: t(4;19)(q25;q13) EXAMPLE: Common (CIC-rearranged sarcoma) EXAMPLE: D EXAMPLE:

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).

EXAMPLE: ALK EXAMPLE: ELM4::ALK


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

EXAMPLE: 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. EXAMPLE: N/A EXAMPLE: Rare (Lung adenocarcinoma) EXAMPLE: T EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

EXAMPLE: ABL1 EXAMPLE: N/A EXAMPLE: 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. EXAMPLE: N/A EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) EXAMPLE: D, P, T



MYB or MYBL1 rearrangement

MYB or MYBL1 amplification

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
6q23.3 rearrangement 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 Creates fusion oncogenic protein


Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (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.)

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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE: No EXAMPLE:

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).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE:

Common recurrent secondary finding for t(8;21) (add references).

EXAMPLE:

17

EXAMPLE: Amp EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

EXAMPLE:

ERBB2

EXAMPLE: D, P, T EXAMPLE:

Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.



MYB or MYBL1 copy number variation as identified by chromosomal microarray or FISH

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
6 Amp/Loss/Gain 135502446-135540310 [GRCh37] 6q23.3 Yes Yes Yes[14] [15][16][17]
8 Amp/Loss/Gain 67474410-67525453 [GRCh37] 8q13.1 Yes Yes Unknown [18][19]


Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: 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.)

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T



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)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
6q23.3 hsr;  MYB amplification Scott C. Smith,

PhD, FACMG; SUNY Upstate Medical University

No Unknown Unknown
8q13.1 hsr; MYBL1 amplificationScott C. Smith,

PhD, FACMG; SUNY Upstate Medical University

No Unknown Unknown


Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program


Gene; Genetic Alteration Pathway Pathophysiologic Outcome
MYB/MYBL1 3’-deletion MYB/MYBL1 protooncogene Deregulation of MYB/MYBL1
MYB/MYBL1 amplification MYB/MYBL1 protooncogene Overexpression of MYB/MYBL1


Genetic Diagnostic Testing Methods

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

References

  1. ↑ Slegers, Rutger Juriaan; et al. (2020-03-09). "Low-grade developmental and epilepsy associated brain tumors: a critical update 2020". Acta Neuropathologica Communications. 8 (1): 27. doi:10.1186/s40478-020-00904-x. ISSN 2051-5960. PMC 7063704 Check |pmc= value (help). PMID 32151273 Check |pmid= value (help).
  2. ↑ Bandopadhayay, Pratiti; et al. (2016-03). "MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism". Nature Genetics. 48 (3): 273–282. doi:10.1038/ng.3500. ISSN 1546-1718. PMC 4767685. PMID 26829751. Check date values in: |date= (help)
  3. ↑ Wefers, Annika K.; et al. (2020-01). "Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course". Acta Neuropathologica. 139 (1): 193–209. doi:10.1007/s00401-019-02078-w. ISSN 1432-0533. PMC 7477753 Check |pmc= value (help). PMID 31563982. Check date values in: |date= (help)
  4. ↑ Chiang, Jason; et al. (2019-12). "A single-center study of the clinicopathologic correlates of gliomas with a MYB or MYBL1 alteration". Acta Neuropathologica. 138 (6): 1091–1092. doi:10.1007/s00401-019-02081-1. ISSN 1432-0533. PMC 7467132 Check |pmc= value (help). PMID 31595312. Check date values in: |date= (help)
  5. ↑ Ramkissoon, Lori A.; et al. (2013-05-14). "Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1". Proceedings of the National Academy of Sciences of the United States of America. 110 (20): 8188–8193. doi:10.1073/pnas.1300252110. ISSN 1091-6490. PMC 3657784. PMID 23633565.
  6. ↑ Barinfeld, Orit; et al. (2022). "Genetic Alteration Analysis of IDH1, IDH2, CDKN2A, MYB and MYBL1 in Pediatric Low-Grade Gliomas". Frontiers in Surgery. 9: 880048. doi:10.3389/fsurg.2022.880048. ISSN 2296-875X. PMC 9096721 Check |pmc= value (help). PMID 35574540 Check |pmid= value (help).
  7. ↑ Suh, Ye Yoon; et al. (2023-02-21). "MYB/MYBL1::QKI fusion-positive diffuse glioma". Journal of Neuropathology and Experimental Neurology. 82 (3): 250–260. doi:10.1093/jnen/nlac123. ISSN 1554-6578. PMC 9941827 Check |pmc= value (help). PMID 36592415 Check |pmid= value (help).
  8. ↑ Jain, Payal; et al. (2017-03-04). "MYB-QKI drives childhood brain tumors via tripartite mechanism". Cell Cycle (Georgetown, Tex.). 16 (5): 390–391. doi:10.1080/15384101.2016.1260990. ISSN 1551-4005. PMC 5351923. PMID 27973981.
  9. ↑ Fabbri, Viscardo Paolo; et al. (2022-12). "Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome". Pathologica. 114 (6): 410–421. doi:10.32074/1591-951X-828. ISSN 1591-951X. PMC 9763978 Check |pmc= value (help). PMID 36534420 Check |pmid= value (help). Check date values in: |date= (help)
  10. ↑ Fabbri, Viscardo Paolo; et al. (2022-12). "Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome". Pathologica. 114 (6): 410–421. doi:10.32074/1591-951X-828. ISSN 1591-951X. PMC 9763978 Check |pmc= value (help). PMID 36534420 Check |pmid= value (help). Check date values in: |date= (help)
  11. ↑ Fabbri, Viscardo Paolo; et al. (2022-12). "Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome". Pathologica. 114 (6): 410–421. doi:10.32074/1591-951X-828. ISSN 1591-951X. PMC 9763978 Check |pmc= value (help). PMID 36534420 Check |pmid= value (help). Check date values in: |date= (help)
  12. ↑ Suh, Ye Yoon; et al. (2023-02-21). "MYB/MYBL1::QKI fusion-positive diffuse glioma". Journal of Neuropathology and Experimental Neurology. 82 (3): 250–260. doi:10.1093/jnen/nlac123. ISSN 1554-6578. PMC 9941827 Check |pmc= value (help). PMID 36592415 Check |pmid= value (help).
  13. ↑ Wefers, Annika K.; et al. (2020-01). "Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course". Acta Neuropathologica. 139 (1): 193–209. doi:10.1007/s00401-019-02078-w. ISSN 1432-0533. PMC 7477753 Check |pmc= value (help). PMID 31563982. Check date values in: |date= (help)
  14. ↑ Trkova, Katerina; et al. (2023-09). "DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy". Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery. 39 (9): 2509–2513. doi:10.1007/s00381-023-05976-3. ISSN 1433-0350. PMC PMC10432314 Check |pmc= value (help). PMID 37165121 Check |pmid= value (help). Check date values in: |date= (help)CS1 maint: PMC format (link)
  15. ↑ Ramkissoon, Lori A.; et al. (2013-05-14). "Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1". Proceedings of the National Academy of Sciences of the United States of America. 110 (20): 8188–8193. doi:10.1073/pnas.1300252110. ISSN 1091-6490. PMC 3657784. PMID 23633565.
  16. ↑ Bale, Tejus A.; et al. (2022-07). "The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors". Brain Pathology (Zurich, Switzerland). 32 (4): e13060. doi:10.1111/bpa.13060. ISSN 1750-3639. PMC 9245930 Check |pmc= value (help). PMID 35218102 Check |pmid= value (help). Check date values in: |date= (help)
  17. ↑ Trkova, Katerina; et al. (2023-09). "DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy". Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery. 39 (9): 2509–2513. doi:10.1007/s00381-023-05976-3. ISSN 1433-0350. PMC PMC10432314 Check |pmc= value (help). PMID 37165121 Check |pmid= value (help). Check date values in: |date= (help)CS1 maint: PMC format (link)
  18. ↑ Ramkissoon, Lori A.; et al. (2013-05-14). "Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1". Proceedings of the National Academy of Sciences of the United States of America. 110 (20): 8188–8193. doi:10.1073/pnas.1300252110. ISSN 1091-6490. PMC 3657784. PMID 23633565.
  19. ↑ Bale, Tejus A.; et al. (2022-07). "The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors". Brain Pathology (Zurich, Switzerland). 32 (4): e13060. doi:10.1111/bpa.13060. ISSN 1750-3639. PMC 9245930 Check |pmc= value (help). PMID 35218102 Check |pmid= value (help). Check date values in: |date= (help)

Notes

*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 Associate Editor 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.

Prior Author(s): *Citation of this Page: “Diffuse astrocytoma, MYB- or MYBL1-altered”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/24/2025, https://ccga.io/index.php/CNS5:Diffuse astrocytoma, MYB- or MYBL1-altered.

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