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| {{DISPLAYTITLE:Diffuse hemispheric glioma, H3 G34-mutant}} | | {{DISPLAYTITLE:Diffuse hemispheric glioma, H3 G34-mutant}} |
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| [[CNS5:Table_of_Contents|Central Nervous System Tumours(WHO Classification, 5th ed.)]] | | [[CNS5:Table_of_Contents|Central Nervous System Tumours(WHO Classification, 5th ed.)]] |
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| Xiaolin Hu, PhD, Sema4 OpCo Inc. | | Xiaolin Hu, PhD, Sema4 OpCo Inc. |
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| ==Gene Rearrangements== | | ==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>
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| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| !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 |
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| |<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)
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| |<span class="blue-text">EXAMPLE:</span> Common (CML)
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| |<span class="blue-text">EXAMPLE:</span> D, P, T
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| |<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
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| |<span class="blue-text">EXAMPLE:</span>
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| 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).
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| |-
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| |<span class="blue-text">EXAMPLE:</span> ''CIC''
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| |<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
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| |<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''.
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| |<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
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| |<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
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| |<span class="blue-text">EXAMPLE:</span> D
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| |<span class="blue-text">EXAMPLE:</span>
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| ''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).
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| |-
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| |<span class="blue-text">EXAMPLE:</span> ''ALK''
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| |<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
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| Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
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| |<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.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
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| |<span class="blue-text">EXAMPLE:</span> T
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| |<span class="blue-text">EXAMPLE:</span>
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| Both balanced and unbalanced forms are observed by FISH (add references).
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| |-
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| |<span class="blue-text">EXAMPLE:</span> ''ABL1''
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<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.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
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| |<span class="blue-text">EXAMPLE:</span> D, P, T
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| |} | | |} |
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| Not applicable
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| {| class="wikitable sortable"
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| !Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
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| !Diagnostic Significance (Yes, No or Unknown)
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| !Prognostic Significance (Yes, No or Unknown)
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| !Therapeutic Significance (Yes, No or Unknown)
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| !Notes
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| |-
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| |N/A||N/A
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| |N/A
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| |N/A
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| |N/A
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| |N/A
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| |N/A
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| |N/A
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| |}
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| ==Individual Region Genomic Gain/Loss/LOH== | | ==Individual Region Genomic Gain/Loss/LOH== |
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| ==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>
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| {| class="wikitable sortable"
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| !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
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| |-
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| |<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
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| |<span class="blue-text">EXAMPLE:</span> MAPK signaling
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| |<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
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| |<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
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| |<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
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| |<span class="blue-text">EXAMPLE:</span> Unregulated cell division
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| |-
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| |<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
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| |<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
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| |<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
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| |-
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| |}
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| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| Prior Author(s): | | Prior Author(s): |
| <nowiki>*</nowiki>''Citation of this Page'': “Diffuse hemispheric glioma, H3 G34-mutant”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Diffuse hemispheric glioma, H3 G34-mutant</nowiki>. | | <nowiki>*</nowiki>''Citation of this Page'': “Diffuse hemispheric glioma, H3 G34-mutant”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Diffuse hemispheric glioma, H3 G34-mutant</nowiki>. |
| [[Category:CNS5]][[Category:DISEASE]][[Category:Diseases D]] | | [[Category:CNS5]] |
| | [[Category:DISEASE]] |
| | [[Category:Diseases D]] |
| | <references /> |
