Compendium of Cancer Genome Aberrations

STBT5:Infantile fibrosarcoma: Difference between revisions

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{{DISPLAYTITLE:Infantile fibrosarcoma}}
{{DISPLAYTITLE:Infantile fibrosarcoma}}
[[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}}
<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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|}
|}


==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
==Related Terminology==


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==Gene Rearrangements==
==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"
{| class="wikitable sortable"
|-
|-
Line 64: Line 46:
!Clinical Relevance Details/Other Notes
!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)
|''NTRK3''||''ETV6''||In-frame fusion that results in constitutive activation of the NTRK3 tyrosine kinase domain through heterodimerization and transphosphorylation of the helix-loop-helix domain of ETV6.<ref name=":1">{{Cite journal|last=Aepala|first=Megha R.|last2=Peiris|first2=Malalage N.|last3=Jiang|first3=Zian|last4=Yang|first4=Wei|last5=Meyer|first5=April N.|last6=Donoghue|first6=Daniel J.|date=2022-12|title=Nefarious NTRK oncogenic fusions in pediatric sarcomas: Too many to Trk|url=https://pubmed.ncbi.nlm.nih.gov/36153202|journal=Cytokine & Growth Factor Reviews|volume=68|pages=93–106|doi=10.1016/j.cytogfr.2022.08.003|issn=1879-0305|pmid=36153202}}</ref> Breakpoints typically involve exon 5 of ''ETV6'' (NM_001987.4) and exons 14 or 15 of ''NTRK3'' (NM_001243101.1).<ref name=":6">{{Cite journal|last=Church|first=Alanna J.|last2=Calicchio|first2=Monica L.|last3=Nardi|first3=Valentina|last4=Skalova|first4=Alena|last5=Pinto|first5=Andre|last6=Dillon|first6=Deborah A.|last7=Gomez-Fernandez|first7=Carmen R.|last8=Manoj|first8=Namitha|last9=Haimes|first9=Josh D.|date=2018-03|title=Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy|url=https://pubmed.ncbi.nlm.nih.gov/29099503|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=31|issue=3|pages=463–473|doi=10.1038/modpathol.2017.127|issn=1530-0285|pmid=29099503}}</ref>||t(12;15)(p13;q25)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|Common
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
|The ''ETV6::NTRK3'' fusion [t(12;15)] is diagnostic of infantile fibrosarcoma in the appropriate morphology and clinical context.<ref name=":6" /><ref>{{Cite journal|last=Caldwell|first=Kenneth J.|last2=De La Cuesta|first2=Esther|last3=Morin|first3=Cara|last4=Pappo|first4=Alberto|last5=Helmig|first5=Sara|date=2020-09|title=A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib|url=https://pubmed.ncbi.nlm.nih.gov/32452122|journal=Pediatric Blood & Cancer|volume=67|issue=9|pages=e28330|doi=10.1002/pbc.28330|issn=1545-5017|pmid=32452122}}</ref><ref name=":3">{{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><ref name=":7">{{Cite journal|last=Rubin|first=B. P.|last2=Chen|first2=C. J.|last3=Morgan|first3=T. W.|last4=Xiao|first4=S.|last5=Grier|first5=H. E.|last6=Kozakewich|first6=H. P.|last7=Perez-Atayde|first7=A. R.|last8=Fletcher|first8=J. A.|date=1998-11|title=Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma|url=https://pubmed.ncbi.nlm.nih.gov/9811336|journal=The American Journal of Pathology|volume=153|issue=5|pages=1451–1458|doi=10.1016/S0002-9440(10)65732-X|issn=0002-9440|pmc=1853403|pmid=9811336}}</ref> This fusion is found in the majority of infantile fibrosarcoma cases. Studies have demonstrated that this fusion is sensitive to TRK inhibitors.<ref>{{Cite journal|last=Cardesa-Salzmann|first=Teresa M.|last2=Sparber-Sauer|first2=Monika|last3=Hingst|first3=Peter|last4=Erbersdobler|first4=Andreas|last5=Schneider|first5=Bjoern|last6=Hühns|first6=Maja|last7=Jakob|first7=Andre|last8=Terpe|first8=Friederike|last9=Spang|first9=Christian|date=2025-05|title=On TRacK With Larotrectinib in a Neonate With a Giant Congenital ETV6::NTRK3 Fusion-Positive Infantile Fibrosarcoma of the Head and Neck|url=https://pubmed.ncbi.nlm.nih.gov/39737858|journal=Head & Neck|volume=47|issue=5|pages=E50–E57|doi=10.1002/hed.28058|issn=1097-0347|pmc=12038221|pmid=39737858}}</ref><ref name=":8">{{Cite journal|last=Hong|first=D. S.|last2=Xu|first2=R.-H.|last3=Shen|first3=L.|last4=Dierselhuis|first4=M. P.|last5=Orbach|first5=D.|last6=McDermott|first6=R.|last7=Italiano|first7=A.|last8=Tahara|first8=M.|last9=Bernard-Gauthier|first9=V.|date=2025-06|title=Efficacy and safety of larotrectinib as first-line treatment for patients with TRK fusion cancer|url=https://pubmed.ncbi.nlm.nih.gov/40408921|journal=ESMO open|volume=10|issue=6|pages=105110|doi=10.1016/j.esmoop.2025.105110|issn=2059-7029|pmc=12151180|pmid=40408921}}</ref><ref name=":9">{{Cite journal|last=Drilon|first=Alexander|last2=Laetsch|first2=Theodore W.|last3=Kummar|first3=Shivaani|last4=DuBois|first4=Steven G.|last5=Lassen|first5=Ulrik N.|last6=Demetri|first6=George D.|last7=Nathenson|first7=Michael|last8=Doebele|first8=Robert C.|last9=Farago|first9=Anna F.|date=2018-02-22|title=Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children|url=https://pubmed.ncbi.nlm.nih.gov/29466156|journal=The New England Journal of Medicine|volume=378|issue=8|pages=731–739|doi=10.1056/NEJMoa1714448|issn=1533-4406|pmc=5857389|pmid=29466156}}</ref><ref name=":10">{{Cite journal|last=Hong|first=David S.|last2=DuBois|first2=Steven G.|last3=Kummar|first3=Shivaani|last4=Farago|first4=Anna F.|last5=Albert|first5=Catherine M.|last6=Rohrberg|first6=Kristoffer S.|last7=van Tilburg|first7=Cornelis M.|last8=Nagasubramanian|first8=Ramamoorthy|last9=Berlin|first9=Jordan D.|date=2020-04|title=Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials|url=https://pubmed.ncbi.nlm.nih.gov/32105622|journal=The Lancet. Oncology|volume=21|issue=4|pages=531–540|doi=10.1016/S1470-2045(19)30856-3|issn=1474-5488|pmc=7497841|pmid=32105622}}</ref><ref name=":11">{{Cite journal|last=Laetsch|first=Theodore W.|last2=Voss|first2=Stephan|last3=Ludwig|first3=Kathleen|last4=Hall|first4=David|last5=Barkauskas|first5=Donald A.|last6=DuBois|first6=Steven G.|last7=Ronan|first7=Joan|last8=Rudzinski|first8=Erin R.|last9=Memken|first9=Amanda|date=2025-04|title=Larotrectinib for Newly Diagnosed Infantile Fibrosarcoma and Other Pediatric NTRK Fusion-Positive Solid Tumors (Children's Oncology Group ADVL1823)|url=https://pubmed.ncbi.nlm.nih.gov/39652801|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=43|issue=10|pages=1188–1197|doi=10.1200/JCO-24-01854|issn=1527-7755|pmc=11954674|pmid=39652801}}</ref>
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).
|-
|''NTRK3''
|''EML4''
|In-frame fusion that is predicted to result in constitutive activation of the NTRK3 tyrosine kinase domain through autodimerization of EML4.<ref name=":1" /> Breakpoints typically involve exon 2 of ''EML4'' (NM_0019063.4) and exons 14 of ''NTRK3'' (NM_001243101.1).<ref name=":6" />
|None
|Recurrent
|D, T
|Yes (WHO)
|The ''EML4::NTRK3'' fusion is diagnostic of infantile fibrosarcoma in the appropriate morphology and clinical context.<ref name=":6" /><ref name=":3" /><ref name=":2">{{Cite journal|last=Davis|first=Jessica L.|last2=Lockwood|first2=Christina M.|last3=Albert|first3=Catherine M.|last4=Tsuchiya|first4=Karen|last5=Hawkins|first5=Douglas S.|last6=Rudzinski|first6=Erin R.|date=2018|title=Infantile NTRK-associated Mesenchymal Tumors|url=https://pubmed.ncbi.nlm.nih.gov/28683589|journal=Pediatric and Developmental Pathology: The Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society|volume=21|issue=1|pages=68–78|doi=10.1177/1093526617712639|issn=1093-5266|pmid=28683589}}</ref><ref name=":12">{{Cite journal|last=Kao|first=Yu-Chien|last2=Fletcher|first2=Christopher D. M.|last3=Alaggio|first3=Rita|last4=Wexler|first4=Leonard|last5=Zhang|first5=Lei|last6=Sung|first6=Yun-Shao|last7=Orhan|first7=Dicle|last8=Chang|first8=Wei-Chin|last9=Swanson|first9=David|date=2018-01|title=Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma|url=https://pubmed.ncbi.nlm.nih.gov/28877062|journal=The American Journal of Surgical Pathology|volume=42|issue=1|pages=28–38|doi=10.1097/PAS.0000000000000938|issn=1532-0979|pmc=5730460|pmid=28877062}}</ref> Studies have demonstrated that this fusion is sensitive to TRK inhibitors.<ref name=":8" /><ref name=":10" /><ref name=":11" />
|-
|''NTRK1''
|''LMNA, TPM3, SQSTM1, MIR584F1''
|In-frame fusion that is predicted to result in constitutive activation of the NTRK1 tyrosine kinase domain likely through dimerization of the 5' fusion partner.<ref name=":1" />
|None
|Recurrent
|D, T
|Yes (WHO)
|''NTRK1'' fusions may be diagnostic of infantile fibrosarcoma in the appropriate morphology and clinical context.<ref name=":2" /><ref name=":12" /><ref>{{Cite journal|last=Pavlick|first=Dean|last2=Schrock|first2=Alexa B.|last3=Malicki|first3=Denise|last4=Stephens|first4=Philip J.|last5=Kuo|first5=Dennis J.|last6=Ahn|first6=Hyunah|last7=Turpin|first7=Brian|last8=Allen|first8=Justin M.|last9=Rosenzweig|first9=Mark|date=2017-08|title=Identification of NTRK fusions in pediatric mesenchymal tumors|url=https://pubmed.ncbi.nlm.nih.gov/28097808|journal=Pediatric Blood & Cancer|volume=64|issue=8|doi=10.1002/pbc.26433|issn=1545-5017|pmid=28097808}}</ref> Studies have demonstrated that NTRK1 fusions are sensitive to TRK inhibitors.<ref name=":8" /><ref name=":9" /><ref name=":10" /><ref name=":11" />
|-
|''NTRK3''
|''SPECC1L''
|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>
|None
|Rare
|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 with excellent clinical response.<ref name=":4" />
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|''BRAF''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|''SEPT7, CUX1''
|<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''.
|In-frame fusion that is predicted to result in activation of the BRAF tyrosine kinase domain.<ref name=":12" />
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|None
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|Rare
|<span class="blue-text">EXAMPLE:</span> D
|D
|
|No
|<span class="blue-text">EXAMPLE:</span>
|Five individuals with unclassified spindle cell sarcomas with features overlapping infantile fibrosarcoma were identified as having a ''BRAF'' rearrangement. ''BRAF'' rearrangement was identified by FISH in 3 patients, while a ''SEPT7::BRAF'' and ''CUX1::BRAF'' fusion were observed in an additional 2 tumors using next generation sequencing.<ref name=":12" /> Although ''BRAF'' fusions are targetable in other tumor types, the utility of targeted therapy in this setting requires further study.
 
''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''
|''BRAF''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|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 name=":3" />
 
|None
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|Rare
|<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
|<span class="blue-text">EXAMPLE:</span> N/A
|No
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|An intragenic rearrangement within ''BRAF'' was identified in a single individual with infantile fibrosarcoma.<ref name=":3" /> Although ''BRAF'' fusions are targetable in other tumor types, the utility of targeted therapy in this setting requires further study.
|<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''
|''RET''
|<span class="blue-text">EXAMPLE:</span> N/A
|''CLIP2, MYH10''
|<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 is predicted to result in activation of the BRAF tyrosine kinase domain. All reported cases demonstrated a breakpoint in exon 12 of ''RET'' (NM_020975.4), retaining the entire tyrosine kinase domain.
|<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
|
|No
|
|SIx patients in total have been reported with a tumor demonstrating IFS-like histology and a ''RET'' fusion (''CLIP2'' n=2, ''MYH10'' n=4).<ref>{{Cite journal|last=Davis|first=Jessica L.|last2=Vargas|first2=Sara O.|last3=Rudzinski|first3=Erin R.|last4=López Marti|first4=Jessica M.|last5=Janeway|first5=Katherine|last6=Forrest|first6=Suzanne|last7=Winsnes|first7=Katrina|last8=Pinto|first8=Navin|last9=Yang|first9=Sung E.|date=2020-06|title=Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/31994201|journal=Histopathology|volume=76|issue=7|pages=1032–1041|doi=10.1111/his.14082|issn=1365-2559|pmid=31994201}}</ref><ref>{{Cite journal|last=Antonescu|first=Cristina R.|last2=Dickson|first2=Brendan C.|last3=Swanson|first3=David|last4=Zhang|first4=Lei|last5=Sung|first5=Yun-Shao|last6=Kao|first6=Yu-Chien|last7=Chang|first7=Wei-Chin|last8=Ran|first8=Leili|last9=Pappo|first9=Alberto|date=2019-10|title=Spindle Cell Tumors With RET Gene Fusions Exhibit a Morphologic Spectrum Akin to Tumors With NTRK Gene Fusions|url=https://pubmed.ncbi.nlm.nih.gov/31219820|journal=The American Journal of Surgical Pathology|volume=43|issue=10|pages=1384–1391|doi=10.1097/PAS.0000000000001297|issn=1532-0979|pmc=6742579|pmid=31219820}}</ref> The utility of RET targeted therapy in this setting requires further study.
|-
|-
|
|''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==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
Whole chromosome gain of 8, 11, 17, and/or 20 (in various combinations) are commonly observed in infantile fibrosarcoma. Copy number findings alone and in the absence of appropriate histopathology and/or diagnostic gene fusion are not diagnostic, prognostic, or therapeutic.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|8
7
|Gain
|<span class="blue-text">EXAMPLE:</span> Loss
|Whole chromosome 8
|<span class="blue-text">EXAMPLE:</span>
|Unknown
chr7
|D
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Whole chromosome gain of 8 is commonly observed in infantile fibrosarcoma.<ref name=":6" /><ref name=":7" /><ref name=":2" /><ref name=":0">{{Cite journal|last=Sandberg|first=Avery A.|last2=Bridge|first2=Julia A.|date=2002-01-01|title=Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: congenital (infantile) fibrosarcoma and mesoblastic nephroma|url=https://pubmed.ncbi.nlm.nih.gov/11801301|journal=Cancer Genetics and Cytogenetics|volume=132|issue=1|pages=1–13|doi=10.1016/s0165-4608(01)00528-3|issn=0165-4608|pmid=11801301}}</ref>
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|11
8
|Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|Whole chromosome 11
|<span class="blue-text">EXAMPLE:</span>
|Unknown
chr8
|D
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Whole chromosome gain of 11 is commonly observed in infantile fibrosarcoma.<ref name=":6" /><ref name=":7" /><ref name=":2" /><ref name=":0" />
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|17
17
|Gain
|<span class="blue-text">EXAMPLE:</span> Amp
|Whole chromosome 17
|<span class="blue-text">EXAMPLE:</span>
|Unknown
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|D
|<span class="blue-text">EXAMPLE:</span>
|No
''ERBB2''
|Whole chromosome gain of 17 is commonly observed in infantile fibrosarcoma.<ref name=":6" /><ref name=":7" /><ref name=":2" /><ref name=":0" />
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|-
|
|20
|
|Gain
|
|Whole chromosome 20
|
|Unknown
|
|D
|
|No
|
|Whole chromosome gain of 20 is commonly observed in infantile fibrosarcoma.<ref name=":6" /><ref name=":7" /><ref name=":2" /><ref name=":0" />
|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. 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>
None
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 179: Line 168:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|N/A
Co-deletion of 1p and 18q
|N/A
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|N/A
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|N/A
|<span class="blue-text">EXAMPLE:</span> D, P
|N/A
|
|N/A
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
None
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 212: Line 185:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|N/A
 
|N/A
<br />
|N/A
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|N/A
|<span class="blue-text">EXAMPLE:</span> Oncogene
|N/A
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|N/A
|<span class="blue-text">EXAMPLE:</span> T
|N/A
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
==Epigenomic Alterations==
Put your text here
None
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|''NTRK1/2/3''; Activating fusion
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|RAS/MAPK signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Increased cell growth and proliferation
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
|
|
|
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
 
#'''Fusion testing'''
#*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
#*Whole transcriptome RNA-sequencing
#**Provides an unbiased approach to fusion calling
#'''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. Consider other fusion partners is ''ETV6'' FISH is negative.
#'''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 SNV/indels for infantile fibrosarcoma
 
==Familial Forms==
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
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>
None
==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
[[Category:STBT5]]
[[Category:DISEASE]]
[[Category:Diseases I]]
<references />
==Notes==
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  


Prior Author(s):
<nowiki>*</nowiki>''Citation of this Page'': “Infantile fibrosarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/STBT5:Infantile fibrosarcoma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Infantile fibrosarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/STBT5:Infantile fibrosarcoma</nowiki>.
[[Category:STBT5]][[Category:DISEASE]][[Category:Diseases I]]
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