Compendium of Cancer Genome Aberrations

HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion: Difference between revisions

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==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL<ref>WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print](5th ed.), International Agency for Research on Cancer (2022)</ref>.
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
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|N/A
|dup(1q)
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|del(6q)
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</blockquote>
</blockquote>
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL<ref>WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print](5th ed.), International Agency for Research on Cancer (2022)</ref>.




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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.
|<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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|}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.
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
Secondary somatic DNA mutations are not frequently seen in ''TCF3-PBX1'' B-ALL. <ref name=":0" />
===Other Mutations===
Secondary somatic copy number aberrations and DNA mutations are not frequently seen in ''TCF3-PBX1'' B-ALL, commonly found additional abnormalities are listed below. <ref name=":0" /><ref name=":2" />
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!Type!!Gene/Region/Other
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|Additional abnormalities||dup(1q), del(6q), +8, i(9q), i(17q), +21
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<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==


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==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


 
''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref><ref name=":0" />
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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|Increased cell-proliferation, survival and chemotaxis
|Increased cell-proliferation, survival and chemotaxis
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<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref><ref name=":0" />
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


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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>
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>
==Additional Information==
==Additional Information==
 
A karyotypically identical t(1;19) has been observed in a subset of B-ALL cases, especially in hyperdiploid B-ALL. This translocation does not involve ''TCF3'' or ''PBX1''. Therefore, a FISH confirmation is often necessary to determine the nature of t(1;19). <ref name=":1" /><ref name=":0" />
*Another translocation involving the ''TCF3'' gene is t(17;19) which results in the fusion of ''HLF'' at 17q22 with ''TCF3''. This variant translocation has been reported in approximately 1% of pediatric B-ALL patients and is associated with a poor prognosis. <ref name=":1" /><ref name=":2" />
*A karyotypically identical t(1;19) has been observed in a subset of B-ALL cases, especially in hyperdiploid B-ALL. This translocation does not involve ''TCF3'' or ''PBX1''. Therefore, a FISH confirmation is often necessary to determine the nature of t(1;19). <ref name=":1" /><ref name=":0" />


==Links==
==Links==
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==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
<references />
 
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==Notes==
==Notes==
Retrieved from "https://content.ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_TCF3::PBX1_fusion"