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| !Established Clinical Significance Per Guidelines - Yes or No (Source) | | !Established Clinical Significance Per Guidelines - Yes or No (Source) |
| !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)
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| |<span class="blue-text">EXAMPLE:</span> Common (CML)
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| |<span class="blue-text">EXAMPLE:</span> D, P, T
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| |<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
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| |<span class="blue-text">EXAMPLE:</span>
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| 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''
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| |<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
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| |<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''.
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| |<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
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| |<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
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| |<span class="blue-text">EXAMPLE:</span> D
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| |<span class="blue-text">EXAMPLE:</span>
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| ''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''
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| |<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
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| Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
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| |<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.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
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| |<span class="blue-text">EXAMPLE:</span> T
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| |<span class="blue-text">EXAMPLE:</span>
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| Both balanced and unbalanced forms are observed by FISH (add references).
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| |<span class="blue-text">EXAMPLE:</span> ''ABL1''
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<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.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
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| |<span class="blue-text">EXAMPLE:</span> D, P, T
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| |''CD274 (PD-L1)'' | | |''CD274 (PD-L1)'' |
| |3′-UTR–truncating structural variants (no protein fusion) | | |3′-UTR–truncating structural variants (no protein fusion)<ref>{{Cite journal|last=Kataoka|first=Keisuke|last2=Shiraishi|first2=Yuichi|last3=Takeda|first3=Yohei|last4=Sakata|first4=Seiji|last5=Matsumoto|first5=Misako|last6=Nagano|first6=Seiji|last7=Maeda|first7=Takuya|last8=Nagata|first8=Yasunobu|last9=Kitanaka|first9=Akira|date=2016-06-16|title=Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers|url=https://pubmed.ncbi.nlm.nih.gov/27281199|journal=Nature|volume=534|issue=7607|pages=402–406|doi=10.1038/nature18294|issn=1476-4687|pmid=27281199}}</ref> |
| |Loss of 3′-UTR microRNA regulation → PD-L1 overexpression → immune evasion | | |Loss of 3′-UTR microRNA regulation → PD-L1 overexpression → immune evasion |
| |Deletions, inversions, duplications, translocations at '''9p24.1''' disrupting 3′-UTR | | |Deletions, inversions, duplications, translocations at '''9p24.1''' disrupting 3′-UTR |
