Compendium of Cancer Genome Aberrations

HAEM5:B lymphoblastic leukaemia/lymphoma with IGH::IL3 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)
|''IL3''||''IGH::IL3''||Balanced translocation that joins the IGH enhancer (14q32) to the  ''IL3'' gene promoter (5q31.1)<ref>{{Cite journal|last=Meeker|first=T. C.|last2=Hardy|first2=D.|last3=Willman|first3=C.|last4=Hogan|first4=T.|last5=Abrams|first5=J.|date=1990-07-15|title=Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia|url=https://pubmed.ncbi.nlm.nih.gov/2114933|journal=Blood|volume=76|issue=2|pages=285–289|issn=0006-4971|pmid=2114933}}</ref>. This results in IL-3 overexpression that drives the leukemic clone in an autocrine manner and induces eosinophil maturation in the bone marrow and reactive eosinophilia in the peripheral blood<ref>{{Cite journal|last=Knuutila|first=S.|last2=Alitalo|first2=R.|last3=Ruutu|first3=T.|date=1993-12|title=Power of the MAC (morphology-antibody-chromosomes) method in distinguishing reactive and clonal cells: report of a patient with acute lymphatic leukemia, eosinophilia, and t(5;14)|url=https://pubmed.ncbi.nlm.nih.gov/7512364|journal=Genes, Chromosomes & Cancer|volume=8|issue=4|pages=219–223|doi=10.1002/gcc.2870080403|issn=1045-2257|pmid=7512364}}</ref><ref>{{Cite journal|last=Kobayashi|first=Kenichiro|last2=Mizuta|first2=Shumpei|last3=Yamane|first3=Noriko|last4=Ueno|first4=Hiroo|last5=Yoshida|first5=Kenichi|last6=Kato|first6=Itaru|last7=Umeda|first7=Katsutsugu|last8=Hiramatsu|first8=Hidefumi|last9=Suehiro|first9=Minoru|date=2019-01|title=Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30207070|journal=Pediatric Blood & Cancer|volume=66|issue=1|pages=e27449|doi=10.1002/pbc.27449|issn=1545-5017|pmid=30207070}}</ref>.||t(5;14)(q31.1;q32)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<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
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|<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''
 
 
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<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.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
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|<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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|D: This translocation must be detected by karyotyping or FISH
T: N/A
P: Too few cases to  accurately assess prognosis
|No (NCCN)
|A small case series suggested an intermediate prognosis, with a poor response to treatment and high levels of measurable residual disease at the end of induction<ref>{{Cite journal|last=Fournier|first=Benjamin|last2=Balducci|first2=Estelle|last3=Duployez|first3=Nicolas|last4=Clappier|first4=Emmanuelle|last5=Cuccuini|first5=Wendy|last6=Arfeuille|first6=Chloé|last7=Caye-Eude|first7=Aurélie|last8=Delabesse|first8=Eric|last9=Bottollier-Lemallaz Colomb|first9=Elodie|date=2019|title=B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL|url=https://pubmed.ncbi.nlm.nih.gov/31921638|journal=Frontiers in Oncology|volume=9|pages=1374|doi=10.3389/fonc.2019.01374|issn=2234-943X|pmc=6914849|pmid=31921638}}</ref>.
|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
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