CNS5:Diffuse hemispheric glioma, H3 G34-mutant: Difference between revisions
| [checked revision] | [checked revision] |
No edit summary |
No edit summary |
||
| Line 197: | Line 197: | ||
|14% case of G34-DHG <ref name=":5" /> | |14% case of G34-DHG <ref name=":5" /> | ||
|} | |} | ||
==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> | 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> | ||
| Line 235: | Line 233: | ||
|} | |} | ||
'''Add content below into table above''' - | |||
'''Add content below into table above''' - | |||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 277: | Line 272: | ||
|Found in 44% of cases of G34-DHG <ref name=":5" /> | |Found in 44% of cases of G34-DHG <ref name=":5" /> | ||
|} | |} | ||
==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> | 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> | ||
| Line 324: | Line 317: | ||
| | | | ||
|}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. | ||
'''Add content below into table above''' - | |||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
| Line 391: | Line 360: | ||
|} | |} | ||
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) 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 cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) 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== | |||
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 | |||
|- | |||
| | |||
| | |||
| | |||
|} | |||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
| Line 420: | Line 413: | ||
|Facilitate alternative lengthening of telomeres | |Facilitate alternative lengthening of telomeres | ||
|} | |} | ||
==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
| Line 427: | Line 419: | ||
*Pan-cancer sequencing will likely detect concurrent mutations in ''TP53, ATRX, PDGFRA'' etc. | *Pan-cancer sequencing will likely detect concurrent mutations in ''TP53, ATRX, PDGFRA'' etc. | ||
*DNA methylation and gene expression profiling can be used to differentiate G34-DHG with other glioma subgroups. | *DNA methylation and gene expression profiling can be used to differentiate G34-DHG with other glioma subgroups. | ||
*''MGMT'' promoter methylation can be assessed by methylation specific polymerase chain reaction analysis (bisulfite treated DNA undergoes real-time PCR) | *''MGMT'' promoter methylation can be assessed by methylation specific polymerase chain reaction analysis (bisulfite treated DNA undergoes real-time PCR) | ||
==Familial Forms== | ==Familial Forms== | ||
| Line 435: | Line 427: | ||
This disease is <u>defined/characterized</u> as detailed below: | This disease is <u>defined/characterized</u> as detailed below: | ||
* Diffuse hemispheric glioma, H3 G34–mutant (G34-DHG) is a newly recognized tumor entity that is characterized by point mutations in the ''H3-3A'' (''H3-3A'') gene, encoding for histone variant H3.3 <ref name=":0">{{Cite journal|last=Schwartzentruber|first=Jeremy|last2=Korshunov|first2=Andrey|last3=Liu|first3=Xiao-Yang|last4=Jones|first4=David T. W.|last5=Pfaff|first5=Elke|last6=Jacob|first6=Karine|last7=Sturm|first7=Dominik|last8=Fontebasso|first8=Adam M.|last9=Quang|first9=Dong-Anh Khuong|date=2012-01-29|title=Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/22286061|journal=Nature|volume=482|issue=7384|pages=226–231|doi=10.1038/nature10833|issn=1476-4687|pmid=22286061}}</ref><ref>{{Cite journal|last=Wu|first=Gang|last2=Broniscer|first2=Alberto|last3=McEachron|first3=Troy A.|last4=Lu|first4=Charles|last5=Paugh|first5=Barbara S.|last6=Becksfort|first6=Jared|last7=Qu|first7=Chunxu|last8=Ding|first8=Li|last9=Huether|first9=Robert|date=2012-01-29|title=Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas|url=https://pubmed.ncbi.nlm.nih.gov/22286216|journal=Nature Genetics|volume=44|issue=3|pages=251–253|doi=10.1038/ng.1102|issn=1546-1718|pmc=3288377|pmid=22286216}}</ref>. Point mutations tend to be clustered at codon 34 including c.103G>A p.G35R (G34R), c.103G>C p.G35R (G34R), or rarely c.104G>T p.G35V (G34V) <ref name=":0" />. This distinct tumor entity is an aggressive glioma arising from the cerebral hemispheres. G34-DHG is designated as CNS WHO grade 4 in in the WHO 5th edition <ref name=":3" />. | *Diffuse hemispheric glioma, H3 G34–mutant (G34-DHG) is a newly recognized tumor entity that is characterized by point mutations in the ''H3-3A'' (''H3-3A'') gene, encoding for histone variant H3.3 <ref name=":0">{{Cite journal|last=Schwartzentruber|first=Jeremy|last2=Korshunov|first2=Andrey|last3=Liu|first3=Xiao-Yang|last4=Jones|first4=David T. W.|last5=Pfaff|first5=Elke|last6=Jacob|first6=Karine|last7=Sturm|first7=Dominik|last8=Fontebasso|first8=Adam M.|last9=Quang|first9=Dong-Anh Khuong|date=2012-01-29|title=Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/22286061|journal=Nature|volume=482|issue=7384|pages=226–231|doi=10.1038/nature10833|issn=1476-4687|pmid=22286061}}</ref><ref>{{Cite journal|last=Wu|first=Gang|last2=Broniscer|first2=Alberto|last3=McEachron|first3=Troy A.|last4=Lu|first4=Charles|last5=Paugh|first5=Barbara S.|last6=Becksfort|first6=Jared|last7=Qu|first7=Chunxu|last8=Ding|first8=Li|last9=Huether|first9=Robert|date=2012-01-29|title=Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas|url=https://pubmed.ncbi.nlm.nih.gov/22286216|journal=Nature Genetics|volume=44|issue=3|pages=251–253|doi=10.1038/ng.1102|issn=1546-1718|pmc=3288377|pmid=22286216}}</ref>. Point mutations tend to be clustered at codon 34 including c.103G>A p.G35R (G34R), c.103G>C p.G35R (G34R), or rarely c.104G>T p.G35V (G34V) <ref name=":0" />. This distinct tumor entity is an aggressive glioma arising from the cerebral hemispheres. G34-DHG is designated as CNS WHO grade 4 in in the WHO 5th edition <ref name=":3" />. | ||
* Please note that historically, numbering of the amino acid sequences of histone genes has begun at the second codon, as the amino acid encoded by the first codon (methionine) is cleaved post-translationally. Therefore, H3.3 G34 represents the legacy nomenclature of what is now referred to as H3.3 G35 <ref>{{Cite journal|last=Leske|first=Henning|last2=Dalgleish|first2=Raymond|last3=Lazar|first3=Alexander J.|last4=Reifenberger|first4=Guido|last5=Cree|first5=Ian A.|date=2021-06|title=A common classification framework for histone sequence alterations in tumours: an expert consensus proposal|url=https://pubmed.ncbi.nlm.nih.gov/33779999|journal=The Journal of Pathology|volume=254|issue=2|pages=109–120|doi=10.1002/path.5666|issn=1096-9896|pmid=33779999}}</ref>. | *Please note that historically, numbering of the amino acid sequences of histone genes has begun at the second codon, as the amino acid encoded by the first codon (methionine) is cleaved post-translationally. Therefore, H3.3 G34 represents the legacy nomenclature of what is now referred to as H3.3 G35 <ref>{{Cite journal|last=Leske|first=Henning|last2=Dalgleish|first2=Raymond|last3=Lazar|first3=Alexander J.|last4=Reifenberger|first4=Guido|last5=Cree|first5=Ian A.|date=2021-06|title=A common classification framework for histone sequence alterations in tumours: an expert consensus proposal|url=https://pubmed.ncbi.nlm.nih.gov/33779999|journal=The Journal of Pathology|volume=254|issue=2|pages=109–120|doi=10.1002/path.5666|issn=1096-9896|pmid=33779999}}</ref>. | ||
The <u>epidemiology/prevalence</u> of this disease is detailed below: | The <u>epidemiology/prevalence</u> of this disease is detailed below: | ||
* G34-DHG is reported to account for approximately 15% of high grade gliomas (HGSs) and typically affect adolescents and young adults with a median age at diagnosis of 15.8 years old <ref>{{Cite journal|last=Picart|first=Thiébaud|last2=Barritault|first2=Marc|last3=Poncet|first3=Delphine|last4=Berner|first4=Lise-Prune|last5=Izquierdo|first5=Cristina|last6=Tabouret|first6=Emeline|last7=Figarella-Branger|first7=Dominique|last8=Idbaïh|first8=Ahmed|last9=Bielle|first9=Franck|date=2021-01|title=Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults|url=https://pubmed.ncbi.nlm.nih.gov/34056608|journal=Neuro-Oncology Advances|volume=3|issue=1|pages=vdab061|doi=10.1093/noajnl/vdab061|issn=2632-2498|pmc=8156974|pmid=34056608}}</ref><ref name=":1" />. Studies have shown that there is a gender difference with male to female ratio of 1.4:1 <ref name=":4" /><ref>{{Cite journal|last=Mackay|first=Alan|last2=Burford|first2=Anna|last3=Carvalho|first3=Diana|last4=Izquierdo|first4=Elisa|last5=Fazal-Salom|first5=Janat|last6=Taylor|first6=Kathryn R.|last7=Bjerke|first7=Lynn|last8=Clarke|first8=Matthew|last9=Vinci|first9=Mara|date=2017-10-09|title=Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma|url=https://pubmed.ncbi.nlm.nih.gov/28966033|journal=Cancer Cell|volume=32|issue=4|pages=520–537.e5|doi=10.1016/j.ccell.2017.08.017|issn=1878-3686|pmc=5637314|pmid=28966033}}</ref>. | *G34-DHG is reported to account for approximately 15% of high grade gliomas (HGSs) and typically affect adolescents and young adults with a median age at diagnosis of 15.8 years old <ref>{{Cite journal|last=Picart|first=Thiébaud|last2=Barritault|first2=Marc|last3=Poncet|first3=Delphine|last4=Berner|first4=Lise-Prune|last5=Izquierdo|first5=Cristina|last6=Tabouret|first6=Emeline|last7=Figarella-Branger|first7=Dominique|last8=Idbaïh|first8=Ahmed|last9=Bielle|first9=Franck|date=2021-01|title=Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults|url=https://pubmed.ncbi.nlm.nih.gov/34056608|journal=Neuro-Oncology Advances|volume=3|issue=1|pages=vdab061|doi=10.1093/noajnl/vdab061|issn=2632-2498|pmc=8156974|pmid=34056608}}</ref><ref name=":1" />. Studies have shown that there is a gender difference with male to female ratio of 1.4:1 <ref name=":4" /><ref>{{Cite journal|last=Mackay|first=Alan|last2=Burford|first2=Anna|last3=Carvalho|first3=Diana|last4=Izquierdo|first4=Elisa|last5=Fazal-Salom|first5=Janat|last6=Taylor|first6=Kathryn R.|last7=Bjerke|first7=Lynn|last8=Clarke|first8=Matthew|last9=Vinci|first9=Mara|date=2017-10-09|title=Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma|url=https://pubmed.ncbi.nlm.nih.gov/28966033|journal=Cancer Cell|volume=32|issue=4|pages=520–537.e5|doi=10.1016/j.ccell.2017.08.017|issn=1878-3686|pmc=5637314|pmid=28966033}}</ref>. | ||
The <u>clinical features</u> of this disease are detailed below: | The <u>clinical features</u> of this disease are detailed below: | ||
* Site dependent neurological symptoms including epileptic seizure, focal deficit, increased intracranial hypertension (headache, nausea and vomiting) <ref>{{Cite journal|last=Picart|first=Thiébaud|last2=Barritault|first2=Marc|last3=Poncet|first3=Delphine|last4=Berner|first4=Lise-Prune|last5=Izquierdo|first5=Cristina|last6=Tabouret|first6=Emeline|last7=Figarella-Branger|first7=Dominique|last8=Idbaïh|first8=Ahmed|last9=Bielle|first9=Franck|date=2021|title=Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults|url=https://pubmed.ncbi.nlm.nih.gov/34056608|journal=Neuro-Oncology Advances|volume=3|issue=1|pages=vdab061|doi=10.1093/noajnl/vdab061|issn=2632-2498|pmc=8156974|pmid=34056608}}</ref>. | *Site dependent neurological symptoms including epileptic seizure, focal deficit, increased intracranial hypertension (headache, nausea and vomiting) <ref>{{Cite journal|last=Picart|first=Thiébaud|last2=Barritault|first2=Marc|last3=Poncet|first3=Delphine|last4=Berner|first4=Lise-Prune|last5=Izquierdo|first5=Cristina|last6=Tabouret|first6=Emeline|last7=Figarella-Branger|first7=Dominique|last8=Idbaïh|first8=Ahmed|last9=Bielle|first9=Franck|date=2021|title=Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults|url=https://pubmed.ncbi.nlm.nih.gov/34056608|journal=Neuro-Oncology Advances|volume=3|issue=1|pages=vdab061|doi=10.1093/noajnl/vdab061|issn=2632-2498|pmc=8156974|pmid=34056608}}</ref>. | ||
* Signs and symptoms - epileptic seizure, focal deficit, increased intracranial hypertension | *Signs and symptoms - epileptic seizure, focal deficit, increased intracranial hypertension | ||
The <u>sites of involvement</u> of this disease are detailed below: | The <u>sites of involvement</u> of this disease are detailed below: | ||