Compendium of Cancer Genome Aberrations

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

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==Primary Author(s)*==
==Primary Author(s)*==


Binu Porath, PhD. Vanderbilt University Medical Center, Nashville, TN
Miguel Gonzalez Mancera, MD
 
Linda D. Cooley, MD, MBA. Children's Mercy Kansas City, Kansas City, MO
==WHO Classification of Disease==
==WHO Classification of Disease==


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!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)
|''TCF3::PBX1'' fusion protein||''TCF3::PBX1''||The ''TCF3''::''PBX1'' fusion results in the production of a fusion protein that has an oncogenic role as a transcriptional activator; it also probably interferes with the normal function of the transcription factors encoded by ''TCF3'' and ''PBX1''<ref>{{Cite journal|last=LeBrun|first=David P.|date=2003-05-01|title=E2A basic helix-loop-helix transcription factors in human leukemia|url=https://pubmed.ncbi.nlm.nih.gov/12700034|journal=Frontiers in Bioscience: A Journal and Virtual Library|volume=8|pages=s206–222|doi=10.2741/1030|issn=1093-9946|pmid=12700034}}</ref>||t(1;19)(q23;q13.3)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|Common
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D: Demonstration of ''TCF3''::''PBX1'' rearrangement
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
P: Associated with intermediate to relatively favorable clinical outcomes<ref>{{Cite journal|last=Burmeister|first=Thomas|last2=Gökbuget|first2=Nicola|last3=Schwartz|first3=Stefan|last4=Fischer|first4=Lars|last5=Hubert|first5=Daniela|last6=Sindram|first6=Annette|last7=Hoelzer|first7=Dieter|last8=Thiel|first8=Eckhard|date=2010-02|title=Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/19713226|journal=Haematologica|volume=95|issue=2|pages=241–246|doi=10.3324/haematol.2009.011346|issn=1592-8721|pmc=2817026|pmid=19713226}}</ref><ref>{{Cite journal|last=Felice|first=María S.|last2=Gallego|first2=Marta S.|last3=Alonso|first3=Cristina N.|last4=Alfaro|first4=Elizabeth M.|last5=Guitter|first5=Myriam R.|last6=Bernasconi|first6=Andrea R.|last7=Rubio|first7=Patricia L.|last8=Zubizarreta|first8=Pedro A.|last9=Rossi|first9=Jorge G.|date=2011-07|title=Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols|url=https://pubmed.ncbi.nlm.nih.gov/21534874|journal=Leukemia & Lymphoma|volume=52|issue=7|pages=1215–1221|doi=10.3109/10428194.2011.565436|issn=1029-2403|pmid=21534874}}</ref><ref>{{Cite journal|last=Lin|first=Anna|last2=Cheng|first2=Frankie W. T.|last3=Chiang|first3=Alan K. S.|last4=Luk|first4=Chung-Wing|last5=Li|first5=Rever C. H.|last6=Ling|first6=Alvin S. C.|last7=Cheuk|first7=Daniel K. L.|last8=Chang|first8=Kai-On|last9=Ku|first9=Dennis|date=2018-12|title=Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong|url=https://pubmed.ncbi.nlm.nih.gov/30051646|journal=Pediatric Blood & Cancer|volume=65|issue=12|pages=e27346|doi=10.1002/pbc.27346|issn=1545-5017|pmid=30051646}}</ref><ref>{{Cite journal|last=Yilmaz|first=Musa|last2=Kantarjian|first2=Hagop M.|last3=Toruner|first3=Gokce|last4=Yin|first4=C. Cameron|last5=Kanagal-Shamanna|first5=Rashmi|last6=Cortes|first6=Jorge E.|last7=Issa|first7=Ghayyas|last8=Short|first8=Nicholas J.|last9=Khoury|first9=Joseph D.|date=2021-01|title=Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis|url=https://pubmed.ncbi.nlm.nih.gov/32955970|journal=Leukemia & Lymphoma|volume=62|issue=1|pages=224–228|doi=10.1080/10428194.2020.1824071|issn=1029-2403|pmc=11648456|pmid=32955970}}</ref>
|<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''


 
T: N/A
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|No (NCCN)
|<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.
|There may be an increased relative risk of CNS relapse in these patients<ref>{{Cite journal|last=Jeha|first=S.|last2=Pei|first2=D.|last3=Raimondi|first3=S. C.|last4=Onciu|first4=M.|last5=Campana|first5=D.|last6=Cheng|first6=C.|last7=Sandlund|first7=J. T.|last8=Ribeiro|first8=R. C.|last9=Rubnitz|first9=J. E.|date=2009-08|title=Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1|url=https://pubmed.ncbi.nlm.nih.gov/19282835|journal=Leukemia|volume=23|issue=8|pages=1406–1409|doi=10.1038/leu.2009.42|issn=1476-5551|pmc=2731684|pmid=19282835}}</ref>. Relapsed patients appear to have a dismal prognosis.
|<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
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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.
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>
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>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''PHF6''


<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Transcription factor
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Recurrent<ref>{{Cite journal|last=Ueno|first=Hiroo|last2=Yoshida|first2=Kenichi|last3=Shiozawa|first3=Yusuke|last4=Nannya|first4=Yasuhito|last5=Iijima-Yamashita|first5=Yuka|last6=Kiyokawa|first6=Nobutaka|last7=Shiraishi|first7=Yuichi|last8=Chiba|first8=Kenichi|last9=Tanaka|first9=Hiroko|date=2020-10-27|title=Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/33095873|journal=Blood Advances|volume=4|issue=20|pages=5165–5173|doi=10.1182/bloodadvances.2019001307|issn=2473-9537|pmc=7594377|pmid=33095873}}</ref>
|<span class="blue-text">EXAMPLE:</span> T
|D: N/A
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
T: N/A
|<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).
T: N/A
|No (NCCN)
|
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|''PAX5''
<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|Transcription factor
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|<span class="blue-text">EXAMPLE:</span> P
|
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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.
|-
|<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
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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.


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