HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma: Difference between revisions

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 ==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>
+{| class="wikitable sortable"
+|-
+!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
+!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
+|-
+|<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)
+|<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
+|
+|<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
+|
+|<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
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|
+|}
 Approximately 32-42% of CLL patients are found to have a translocation noted on conventional G-banding cytogenetics<ref name=":3">{{Cite journal|last=Baliakas|first=Panagiotis|last2=Iskas|first2=Michalis|last3=Gardiner|first3=Anne|last4=Davis|first4=Zadie|last5=Plevova|first5=Karla|last6=Nguyen-Khac|first6=Florence|last7=Malcikova|first7=Jitka|last8=Anagnostopoulos|first8=Achilles|last9=Glide|first9=Sharron|date=2014-03|title=Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data|url=https://pubmed.ncbi.nlm.nih.gov/24166834|journal=American Journal of Hematology|volume=89|issue=3|pages=249–255|doi=10.1002/ajh.23618|issn=1096-8652|pmid=24166834}}</ref><ref>{{Cite journal|last=Van Den Neste|first=E.|last2=Robin|first2=V.|last3=Francart|first3=J.|last4=Hagemeijer|first4=A.|last5=Stul|first5=M.|last6=Vandenberghe|first6=P.|last7=Delannoy|first7=A.|last8=Sonet|first8=A.|last9=Deneys|first9=V.|date=2007-08|title=Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine|url=https://pubmed.ncbi.nlm.nih.gov/17541398|journal=Leukemia|volume=21|issue=8|pages=1715–1722|doi=10.1038/sj.leu.2404764|issn=0887-6924|pmid=17541398}}</ref><ref>{{Cite journal|last=Mayr|first=Christine|last2=Speicher|first2=Michael R.|last3=Kofler|first3=David M.|last4=Buhmann|first4=Raymund|last5=Strehl|first5=John|last6=Busch|first6=Raymonde|last7=Hallek|first7=Michael|last8=Wendtner|first8=Clemens-Martin|date=2006-01-15|title=Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/16179374|journal=Blood|volume=107|issue=2|pages=742–751|doi=10.1182/blood-2005-05-2093|issn=0006-4971|pmid=16179374}}</ref>. Balanced translocations involving ''IGH'' are uncommon (4-9% of patients)<ref>{{Cite journal|last=Cavazzini|first=Francesco|last2=Hernandez|first2=Jose Angel|last3=Gozzetti|first3=Alessandro|last4=Russo Rossi|first4=Antonella|last5=De Angeli|first5=Cristiano|last6=Tiseo|first6=Ruana|last7=Bardi|first7=Antonella|last8=Tammiso|first8=Elisa|last9=Crupi|first9=Rosaria|date=2008-08|title=Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/18547320|journal=British Journal of Haematology|volume=142|issue=4|pages=529–537|doi=10.1111/j.1365-2141.2008.07227.x|issn=1365-2141|pmid=18547320}}</ref>.
@@ Line 164: / Line 223: @@
 |Prolymphocytes are detected in most of these cases. MYC translocations are associated with an inferior prognosis<ref>{{Cite journal|last=Put|first=Natalie|last2=Van Roosbroeck|first2=Katrien|last3=Konings|first3=Peter|last4=Meeus|first4=Peter|last5=Brusselmans|first5=Caroline|last6=Rack|first6=Katrina|last7=Gervais|first7=Carine|last8=Nguyen-Khac|first8=Florence|last9=Chapiro|first9=Elise|date=2012-06|title=Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course|url=https://pubmed.ncbi.nlm.nih.gov/22205151|journal=Annals of Hematology|volume=91|issue=6|pages=863–873|doi=10.1007/s00277-011-1393-y|issn=1432-0584|pmid=22205151}}</ref><ref>{{Cite journal|last=Huh|first=Yang O.|last2=Lin|first2=Katherine I.-Chun|last3=Vega|first3=Francisco|last4=Schlette|first4=Ellen|last5=Yin|first5=C. Cameron|last6=Keating|first6=Michael J.|last7=Luthra|first7=R.|last8=Medeiros|first8=L. Jeffrey|last9=Abruzzo|first9=Lynne V.|date=2008-07|title=MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/18477041|journal=British Journal of Haematology|volume=142|issue=1|pages=36–44|doi=10.1111/j.1365-2141.2008.07152.x|issn=1365-2141|pmid=18477041}}</ref>.
 |}
 ==Individual Region Genomic Gain/Loss/LOH==