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| Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
| | Laveniya Satgunaseelan, MBBS BMedSc FRCPA, Royal Prince Alfred Hospital |
| ==WHO Classification of Disease== | | ==WHO Classification of Disease== |
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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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| ==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>
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| ==Characteristic Chromosomal or Other Global Mutational 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>
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| !Clinical Relevance Details/Other Notes | | !Clinical Relevance Details/Other Notes |
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| |<span class="blue-text">EXAMPLE:</span> | | |Co-deletion of 1p and 19q |
| Co-deletion of 1p and 18q | | |Unknown |
| |<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). | | |Recurrent to common |
| |<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma) | | |D |
| |<span class="blue-text">EXAMPLE:</span> D, P | | |Yes (WHO) |
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| | |Prevalence between 18% and 33% (PMIDs: 25720745, 29766299) |
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| |<span class="blue-text">EXAMPLE:</span> | | | colspan="6" | |
| Microsatellite instability - hypermutated
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| |<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
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| |<span class="blue-text">EXAMPLE:</span> P, T
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| |} | | |} |
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| ==Gene Mutations (SNV/INDEL)== | | ==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>
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| !Clinical Relevance Details/Other Notes | | !Clinical Relevance Details/Other Notes |
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| |<span class="blue-text">EXAMPLE:</span>''EGFR'' | | |''BRAF'' |
| | | |p.V600E (activating mutation) |
| | |Oncogene |
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| | |Rare |
| | |D, T |
| | |Yes (WHO, NCCN) |
| | |Rare reports of DLGNTs harboring ''BRAF'' p.V600E mutations (PMIDs: 26994902, 32605662), including abstracts detailing efficacy of BRAF inhibtors in ''BRAF''-mutant DLGNT (PMCID: PMC7715974; <nowiki>https://doi.org/10.1093/neuonc/noaa222.297</nowiki>) |
| <br /> | | <br /> |
| |<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
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| |<span class="blue-text">EXAMPLE:</span> Oncogene
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| |<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
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| |<span class="blue-text">EXAMPLE:</span> T
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| |<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
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| |<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).
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| |- | | |- |
| |<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations | | |''FGFR1'' |
| | |p.N456K |
| | |Oncogene |
| <br /> | | <br /> |
| |<span class="blue-text">EXAMPLE:</span> Variable LOF mutations | | |Rare |
| |<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene | | |D |
| |<span class="blue-text">EXAMPLE:</span> Common (breast cancer) | | |Yes (WHO) |
| |<span class="blue-text">EXAMPLE:</span> P | | |PMID: 27061725 |
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| |<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.
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| |<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations | | |''PIK3CA'' |
| |<span class="blue-text">EXAMPLE:</span> Activating mutations | | |p.E545A |
| |<span class="blue-text">EXAMPLE:</span> Oncogene | | |Oncogene |
| |<span class="blue-text">EXAMPLE:</span> Common (melanoma) | | <br /> |
| |<span class="blue-text">EXAMPLE:</span> T | | |Rare |
| | | | |Nil |
| | | | |No |
| | |PMID: 32605662 |
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| | | | |''TERT'' |
| | | | |Activating mutations in promoter region |
| | | | |Oncogene |
| | | | |Rare |
| | | | |Nil |
| | | | |No |
| | | | |Point mutations described include C228T and C228A (PMID: 29766299) |
| |}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. | | |}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== | | ==Epigenomic Alterations== |
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| | | On methylation profiling of a large series of DLGNTs, two methylation classes have been defined - DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2. All cases of DLGNT-MC-2 exhibited gain of chr1q, with 1p/19q codeletion more common in DLGNT-MC-1 (PMID: 29766299). |
| Put your text here
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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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| !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | | !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome |
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| |<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations | | |''BRAF, FGFR1''; Activating mutations |
| |<span class="blue-text">EXAMPLE:</span> MAPK signaling | | |MAPK signaling |
| |<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation | | |Increased cell growth and proliferation |
| |- | | |- |
| |<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations | | |''FGFR1, PIK3CA''; Activating mutations |
| |<span class="blue-text">EXAMPLE:</span> Cell cycle regulation | | |PI3K–Akt signaling pathway |
| |<span class="blue-text">EXAMPLE:</span> Unregulated cell division | | |Increased cell growth, proliferation, survival and motility |
| |- | | |- |
| |<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations | | | colspan="3" | |
| |<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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| |} | | |} |
| ==Genetic Diagnostic Testing Methods== | | ==Genetic Diagnostic Testing Methods== |
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| | - Fusion detection via targeted NGS (RNA or DNA panels) or FISH |
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| | - Chromosomal alterations can be detected by FISH, SNP array, methylation array or NGS |
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| | - Methylation profiling via CNS tumor classifiers for DLGNT-MCs |
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| Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
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| ==Familial Forms== | | ==Familial Forms== |
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| | One case of DLGNT in which a germline mutation in ''RAF1'' has been documented (PMID: 26994902). |
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| Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
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| ==Additional Information== | | ==Additional Information== |
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