Compendium of Cancer Genome Aberrations

STBT5:Infantile fibrosarcoma: Difference between revisions

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{{DISPLAYTITLE:Infantile fibrosarcoma}}
{{DISPLAYTITLE:Infantile fibrosarcoma}}


W[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]
[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}
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<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
==Primary Author(s)*==
==Primary Author(s)*==
Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
Kathleen Schieffer, PhD, FACMG
==WHO Classification of Disease==
==WHO Classification of Disease==


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|''EML4''
|''EML4''
|<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> 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)
|None
|Recurrent
|Recurrent
|D, T
|D, T
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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).
''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''
|''NTRK1''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|''LMNA, TPM3, SQSTM1, MIR584F1''
 
|<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.
 
|None
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|Recurrent
|<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.
|D, T
|<span class="blue-text">EXAMPLE:</span> N/A
|Yes (WHO)
|<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''
|''NTRK3''
|<span class="blue-text">EXAMPLE:</span> N/A
|''SPECC1L''
|<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.
|In-frame fusion that results in constitutive activation of the NTRK3 tyrosine kinase through heterodimerization and transphosphorylation of the SMC (structural maintenance of chromosomes) domain of SPECC1L. In this case, the breakpoint was in exon 9 of ''SPECC1L'' (NM_015330) and exon 13 of ''NTRK3'' (NM_002530) and encompassed the entire tyrosine kinase domain of NTRK3.<ref name=":4">{{Cite journal|last=Khuong-Quang|first=Dong-Anh|last2=Brown|first2=Lauren M.|last3=Wong|first3=Marie|last4=Mayoh|first4=Chelsea|last5=Sexton-Oates|first5=Alexandra|last6=Kumar|first6=Amit|last7=Pinese|first7=Mark|last8=Nagabushan|first8=Sumanth|last9=Lau|first9=Loretta|date=2020-12|title=Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors|url=https://pubmed.ncbi.nlm.nih.gov/33144287|journal=Cold Spring Harbor Molecular Case Studies|volume=6|issue=6|pages=a005710|doi=10.1101/mcs.a005710|issn=2373-2873|pmc=7784491|pmid=33144287}}</ref>
|<span class="blue-text">EXAMPLE:</span> N/A
|None
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|Rare
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D, T
|
|No
|
|A ''SPECC1L::NTRK3'' fusion was reported in a single individual with a large infantile fibrosarcoma of the chest wall. The patient was treated with a TRK inhibitor (larotrectinib) with excellent clinical response.<ref name=":4" />
|-
|-
|''BRAF''
|''PT7, CUX1''
|
|
|None
|Rare
|
|
|No
|
|
|-
|''BRAF''
|Deletion of CR1 domain and tandem duplication within exon 2
|Intragenic gene rearrangement that is predicted to result in a constitutively active form of BRAF due to loss of the negative regulatory Ras-binding domain.<ref>{{Cite journal|last=Wegert|first=Jenny|last2=Vokuhl|first2=Christian|last3=Collord|first3=Grace|last4=Del Castillo Velasco-Herrera|first4=Martin|last5=Farndon|first5=Sarah J.|last6=Guzzo|first6=Charlotte|last7=Jorgensen|first7=Mette|last8=Anderson|first8=John|last9=Slater|first9=Olga|date=2018-06-18|title=Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants|url=https://pubmed.ncbi.nlm.nih.gov/29915264|journal=Nature Communications|volume=9|issue=1|pages=2378|doi=10.1038/s41467-018-04650-6|issn=2041-1723|pmc=6006309|pmid=29915264}}</ref>
|None
|Rare
|
|
|No
|
|
|-
|''RET''
|''CLIP2, MYH10''
|
|
|None
|Rare
|
|
|No
|
|
|-
|''MET''
|''TFG''
|In-frame fusion that is predicted to result in constitutive action of the MET tyrosine kinase domain through dimerization of the TFG dimerization domains. In this case, the breakpoint was in exon 7 of ''TFG'' and exon 15 of ''MET'' and encompassed the entire tyrosine kinase domain of MET.<ref name=":5">{{Cite journal|last=Flucke|first=Uta|last2=van Noesel|first2=Max M.|last3=Wijnen|first3=Marc|last4=Zhang|first4=Lei|last5=Chen|first5=Chun-Liang|last6=Sung|first6=Yun-Shao|last7=Antonescu|first7=Cristina R.|date=2017-09|title=TFG-MET fusion in an infantile spindle cell sarcoma with neural features|url=https://pubmed.ncbi.nlm.nih.gov/28510278|journal=Genes, Chromosomes & Cancer|volume=56|issue=9|pages=663–667|doi=10.1002/gcc.22470|issn=1098-2264|pmc=5507719|pmid=28510278}}</ref>
|None
|Rare
|D
|Yes (WHO)
|A ''TFG::MET'' fusion was reported in a single individual with an unusual infantile spindle cell sarcoma that morphologically resembled infantile fibrosarcoma. MET IHC showed diffuse expression with moderate intensity and RNA expression analysis indicated an intermediate overexpression of ''MET''.<ref name=":5" />
|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
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==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


* Fusion testing  
*Fusion testing  
** Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels)
**Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels)
*** For targeted NGS panels, consider if the assay requires both gene partners to be included on the panel or if it is able to identify novel fusions as long as one of the partners is included on the panel
***For targeted NGS panels, consider if the assay requires both gene partners to be included on the panel or if it is able to identify novel fusions as long as one of the partners is included on the panel
** Whole transcriptome RNA-sequencing
**Whole transcriptome RNA-sequencing
*** Provides an unbiased approach to fusion calling
***Provides an unbiased approach to fusion calling
* Fluorescence ''in situ'' hybridization (FISH)
*Fluorescence ''in situ'' hybridization (FISH)
** Break apart probes for ''ETV6'' and/or ''NTRK3'' will identify a rearrangement (''ETV6::NTRK3'') present in the majority of infantile fibrosarcoma
**Break apart probes for ''ETV6'' and/or ''NTRK3'' will identify a rearrangement (''ETV6::NTRK3'') present in the majority of infantile fibrosarcoma. Consider other fusion partners is ''ETV6'' FISH is negative.
* Karyotyping - can identify  
*Karyotyping
**Can identify the t(12;15) rearrangement as well as other commonly reported aneusomies (i.e. whole chromosome gains of 8, 11, 17, 20)
*DNA sequencing
**Can identify the commonly reported aneusomies if copy number variant calling is performed
**Currently, there are no recurrently described somatic variants for infantile fibrosarcoma


==Familial Forms==
==Familial Forms==
None
None
==Additional Information==
==Additional Information==
Put your text here
None
==Links==
==Links==
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
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[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases I]]
[[Category:Diseases I]]
<references />
Retrieved from "https://test.ccga.io/index.php/STBT5:Infantile_fibrosarcoma"