HAEM5:NK-large granular lymphocytic leukaemia: Difference between revisions
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==Gene Rearrangements== | ==Gene Rearrangements== | ||
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!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 | |||
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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) | |||
|<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). | |||
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|<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). | |||
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|<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). | |||
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|<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== | ||