CNS5:Ganglioglioma: Difference between revisions - Compendium of Cancer Genome Aberrations

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[[CNS5:Table_of_Contents|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 [https://www.genenames.org/ HUGO-approved gene names and symbols] (italicized when appropriate), [https://varnomen.hgvs.org/ 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 [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)''

==Primary Author(s)*==

Dr Leila Moayed Alaei, Royal Prince Alfred Hospital

~~__TOC__~~

~~==Cancer Category/Type==~~

~~Glioneuronal tumour~~

==WHO Classification of Disease==

=~~=Cancer Sub~~-~~Classification /~~ Subtype==

{| class="wikitable"

!Structure

~~Ganglioglioma~~

!Disease

|-

|Book

|Central Nervous System Tumours (5th ed.)

|-

|Category

|Gliomas, glioneuronal tumours, and neuronal tumours

|-

|Family

|Gliomas, glioneuronal tumours, and neuronal tumours

|-

|Type

|Glioneuronal and neuronal tumours

|-

|Subtype(s)

|Ganglioglioma

|}

==Definition / Description of Disease==

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|}

==~~Chromosomal~~ Rearrangements (Gene Fusions)==

==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.'')

{| 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

|-

|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

|

|-

|

|}

{| class="wikitable"

|'''Chromosomal Rearrangement'''

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|}

==Characteristic Chromosomal Aberrations / Patterns==

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==Gene Mutations (SNV/INDEL)==

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

{| 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'''

|-

|EXAMPLE:''EGFR''

|EXAMPLE: Exon 18-21 activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (lung cancer)

|EXAMPLE: T

|EXAMPLE: Yes (NCCN)

|EXAMPLE: 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).

|-

|EXAMPLE: ''TP53''; Variable LOF mutations

|EXAMPLE: Variable LOF mutations

|EXAMPLE: Tumor Supressor Gene

|EXAMPLE: Common (breast cancer)

|EXAMPLE: P

|

|EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

|-

|EXAMPLE: ''BRAF''; Activating mutations

|EXAMPLE: Activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (melanoma)

|EXAMPLE: T

|

|-

|

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

{| class="wikitable"

|'''Gene; Genetic Alteration'''

Line 439:

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|}

==Epigenomics (Methylation)==

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==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.)''

{| class="wikitable sortable"

|-

!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

|-

|

|}

90% of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />.

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|Increase cell growth and proliferation

|}

==Diagnostic Testing Methods==

Line 489:

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==References==

<nowiki>*</nowiki>''Citation of this Page'': “Ganglioglioma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Ganglioglioma</nowiki>.

[[Category:CNS5]][[Category:DISEASE]][[Category:Diseases G]]

@@ Line 1: / Line 1: @@
+{{DISPLAYTITLE:Ganglioglioma}}
+[[CNS5:Table_of_Contents|Central Nervous System Tumours(WHO Classification, 5th ed.)]]
+{{Under Construction}}
+<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)*==
 Dr Leila Moayed Alaei, Royal Prince Alfred Hospital
-__TOC__
-==Cancer Category/Type==
-Glioneuronal tumour
+==WHO Classification of Disease==
-==Cancer Sub-Classification / Subtype==
+{| class="wikitable"
+!Structure
-Ganglioglioma
+!Disease
+|-
+|Book
+|Central Nervous System Tumours (5th ed.)
+|-
+|Category
+|Gliomas, glioneuronal tumours, and neuronal tumours
+|-
+|Family
+|Gliomas, glioneuronal tumours, and neuronal tumours
+|-
+|Type
+|Glioneuronal and neuronal tumours
+|-
+|Subtype(s)
+|Ganglioglioma
+|}
 ==Definition / Description of Disease==
@@ Line 78: / Line 98: @@
 |}
-==Chromosomal Rearrangements (Gene Fusions)==
+==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
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|
+|}
 {| class="wikitable"
 |'''Chromosomal Rearrangement'''
@@ Line 175: / Line 257: @@
 <br />
 |}
 ==Characteristic Chromosomal Aberrations / Patterns==
@@ Line 364: / Line 448: @@
 <br />
 ==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.
 {| class="wikitable"
 |'''Gene; Genetic Alteration'''
@@ Line 439: / Line 570: @@
 <br />
 |}
 ==Epigenomics (Methylation)==
@@ Line 445: / Line 578: @@
 ==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
+|-
+|
+|
+|
+|}
 % of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />.
@@ Line 472: / Line 629: @@
 |Increase cell growth and proliferation
 |}
 ==Diagnostic Testing Methods==
@@ Line 489: / Line 648: @@
 ==References==
 <references />
+<nowiki>*</nowiki>''Citation of this Page'': “Ganglioglioma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Ganglioglioma</nowiki>.
+[[Category:CNS5]][[Category:DISEASE]][[Category:Diseases G]]