STBT5:Solitary fibrous tumour: Difference between revisions

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{{Under Construction}}
{{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)*==
Reba Daniel and Shashi Shetty
Reba Daniel and Shashi Shetty
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|-
|Not Recommended
|Not Recommended
|solitary fibrous tumour / haemangiopericytoma; haemangiopericytoma
|Solitary fibrous tumour / Haemangiopericytoma; Haemangiopericytoma
|}
|}


==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"
|-
|-
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!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)
|N/A
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|''NAB2''-''STAT6''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|Paracentric inversion results in the fusion.<ref>{{Cite journal|last=Chmielecki|first=Juliann|last2=Crago|first2=Aimee M|last3=Rosenberg|first3=Mara|last4=O'Connor|first4=Rachael|last5=Walker|first5=Sarah R|last6=Ambrogio|first6=Lauren|last7=Auclair|first7=Daniel|last8=McKenna|first8=Aaron|last9=Heinrich|first9=Michael C|date=2013-02|title=Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors|url=https://www.nature.com/articles/ng.2522|journal=Nature Genetics|language=en|volume=45|issue=2|pages=131–132|doi=10.1038/ng.2522|issn=1061-4036}}</ref><ref>{{Cite journal|last=Mohajeri|first=Arezoo|last2=Tayebwa|first2=Johnbosco|last3=Collin|first3=Anna|last4=Nilsson|first4=Jenny|last5=Magnusson|first5=Linda|last6=von Steyern|first6=Fredrik Vult|last7=Brosjö|first7=Otte|last8=Domanski|first8=Henryk A.|last9=Larsson|first9=Olle|date=2013-10|title=Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.22083|journal=Genes, Chromosomes and Cancer|language=en|volume=52|issue=10|pages=873–886|doi=10.1002/gcc.22083|issn=1045-2257}}</ref><ref name=":5">{{Cite journal|last=Robinson|first=Dan R|last2=Wu|first2=Yi-Mi|last3=Kalyana-Sundaram|first3=Shanker|last4=Cao|first4=Xuhong|last5=Lonigro|first5=Robert J|last6=Sung|first6=Yun-Shao|last7=Chen|first7=Chun-Liang|last8=Zhang|first8=Lei|last9=Wang|first9=Rui|date=2013-02|title=Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing|url=https://www.nature.com/articles/ng.2509|journal=Nature Genetics|language=en|volume=45|issue=2|pages=180–185|doi=10.1038/ng.2509|issn=1061-4036}}</ref><ref>{{Cite journal|last=Huang|first=Shih‐Chiang|last2=Li|first2=Chien‐Feng|last3=Kao|first3=Yu‐Chien|last4=Chuang|first4=I‐Chieh|last5=Tai|first5=Hui‐Chun|last6=Tsai|first6=Jen‐Wei|last7=Yu|first7=Shih‐Chen|last8=Huang|first8=Hsuan‐Ying|last9=Lan|first9=Jui|date=2016-02|title=The clinicopathological significance of NAB 2‐ STAT 6  gene fusions in 52 cases of intrathoracic solitary fibrous tumors|url=https://onlinelibrary.wiley.com/doi/10.1002/cam4.572|journal=Cancer Medicine|language=en|volume=5|issue=2|pages=159–168|doi=10.1002/cam4.572|issn=2045-7634}}</ref><ref>{{Cite journal|last=Vogels|first=Rob JC|last2=Vlenterie|first2=Myrella|last3=Versleijen-Jonkers|first3=Yvonne MH|last4=Ruijter|first4=Emiel|last5=Bekers|first5=Elise M|last6=Verdijk|first6=Marian AJ|last7=Link|first7=Monique M|last8=Bonenkamp|first8=Johannes J|last9=van der Graaf|first9=Winette TA|date=2014-12|title=Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases|url=https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-014-0224-6|journal=Diagnostic Pathology|language=en|volume=9|issue=1|doi=10.1186/s13000-014-0224-6|issn=1746-1596}}</ref><ref name=":0">{{Cite journal|last=Akaike|first=Keisuke|last2=Kurisaki-Arakawa|first2=Aiko|last3=Hara|first3=Kieko|last4=Suehara|first4=Yoshiyuki|last5=Takagi|first5=Tatsuya|last6=Mitani|first6=Keiko|last7=Kaneko|first7=Kazuo|last8=Yao|first8=Takashi|last9=Saito|first9=Tsuyoshi|date=2015-03|title=Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817714004912|journal=Human Pathology|language=en|volume=46|issue=3|pages=347–356|doi=10.1016/j.humpath.2014.11.018}}</ref> The fusion is thought to convert wildtype NAB2 from a transcriptional repressor of EGR1-mediated signalling into a transcriptional activator via replacement of the C-terminal repression domain by the transcriptional activation domain of STAT6, thereby resulting in a feedforward loop of constitutive EGR1-mediated transactivation of proliferation and survival-associated growth factors, including ''IGF2'' and ''FGFR1''. <ref name=":5" />
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|inv(12)(q13q13)
|<span class="blue-text">EXAMPLE:</span>
|Common
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).
|D
|-
|Y (WHO)
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|''NAB2''-''STAT6'' gene fusions are pathognomonic for SFT. Many different breakpoints in the exons and introns are associated with this fusion. Ex: ''NAB2''ex4-''STAT6''ex2; ''NAB2''ex6-''STAT6''ex16/17.
|<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
|
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Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|inv(12)(q13q13)||3'STAT6 / 5'NAB2<ref>{{Cite journal|last=Huang|first=Shih‐Chiang|last2=Li|first2=Chien‐Feng|last3=Kao|first3=Yu‐Chien|last4=Chuang|first4=I‐Chieh|last5=Tai|first5=Hui‐Chun|last6=Tsai|first6=Jen‐Wei|last7=Yu|first7=Shih‐Chen|last8=Huang|first8=Hsuan‐Ying|last9=Lan|first9=Jui|date=2016-02|title=The clinicopathological significance of  NAB 2‐ STAT 6  gene fusions in 52 cases of intrathoracic solitary fibrous tumors|url=https://onlinelibrary.wiley.com/doi/10.1002/cam4.572|journal=Cancer Medicine|language=en|volume=5|issue=2|pages=159–168|doi=10.1002/cam4.572|issn=2045-7634}}</ref><ref>{{Cite journal|last=Chmielecki|first=Juliann|last2=Crago|first2=Aimee M|last3=Rosenberg|first3=Mara|last4=O'Connor|first4=Rachael|last5=Walker|first5=Sarah R|last6=Ambrogio|first6=Lauren|last7=Auclair|first7=Daniel|last8=McKenna|first8=Aaron|last9=Heinrich|first9=Michael C|date=2013-02|title=Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors|url=https://www.nature.com/articles/ng.2522|journal=Nature Genetics|language=en|volume=45|issue=2|pages=131–132|doi=10.1038/ng.2522|issn=1061-4036}}</ref><ref>{{Cite journal|last=Robinson|first=Dan R|last2=Wu|first2=Yi-Mi|last3=Kalyana-Sundaram|first3=Shanker|last4=Cao|first4=Xuhong|last5=Lonigro|first5=Robert J|last6=Sung|first6=Yun-Shao|last7=Chen|first7=Chun-Liang|last8=Zhang|first8=Lei|last9=Wang|first9=Rui|date=2013-02|title=Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing|url=https://www.nature.com/articles/ng.2509|journal=Nature Genetics|language=en|volume=45|issue=2|pages=180–185|doi=10.1038/ng.2509|issn=1061-4036}}</ref><ref>{{Cite journal|last=Mohajeri|first=Arezoo|last2=Tayebwa|first2=Johnbosco|last3=Collin|first3=Anna|last4=Nilsson|first4=Jenny|last5=Magnusson|first5=Linda|last6=von Steyern|first6=Fredrik Vult|last7=Brosjö|first7=Otte|last8=Domanski|first8=Henryk A.|last9=Larsson|first9=Olle|date=2013-10|title=Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.22083|journal=Genes, Chromosomes and Cancer|language=en|volume=52|issue=10|pages=873–886|doi=10.1002/gcc.22083|issn=1045-2257}}</ref><ref>{{Cite journal|last=Vogels|first=Rob JC|last2=Vlenterie|first2=Myrella|last3=Versleijen-Jonkers|first3=Yvonne MH|last4=Ruijter|first4=Emiel|last5=Bekers|first5=Elise M|last6=Verdijk|first6=Marian AJ|last7=Link|first7=Monique M|last8=Bonenkamp|first8=Johannes J|last9=van der Graaf|first9=Winette TA|date=2014-12|title=Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases|url=https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-014-0224-6|journal=Diagnostic Pathology|language=en|volume=9|issue=1|doi=10.1186/s13000-014-0224-6|issn=1746-1596}}</ref><ref name=":0">{{Cite journal|last=Akaike|first=Keisuke|last2=Kurisaki-Arakawa|first2=Aiko|last3=Hara|first3=Kieko|last4=Suehara|first4=Yoshiyuki|last5=Takagi|first5=Tatsuya|last6=Mitani|first6=Keiko|last7=Kaneko|first7=Kazuo|last8=Yao|first8=Takashi|last9=Saito|first9=Tsuyoshi|date=2015-03|title=Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817714004912|journal=Human Pathology|language=en|volume=46|issue=3|pages=347–356|doi=10.1016/j.humpath.2014.11.018}}</ref>||NA||55-100%
|Yes
|Unknown
|No
|Many different breakpoints in the exons and introns are associated with this fusion. Ex: ''NAB2''ex4-''STAT6''ex2; ''NAB2''ex6-''STAT6''ex16/17
|}


==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>
None
{| 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>
|N/A
7
|N/A
|<span class="blue-text">EXAMPLE:</span> Loss
|N/A
|<span class="blue-text">EXAMPLE:</span>
|N/A
chr7
|N/A
|<span class="blue-text">EXAMPLE:</span>
|N/A
Unknown
|N/A
|<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>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<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
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<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.
|-
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Not Applicable
{| class="wikitable sortable"
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!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
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==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"
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|-
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!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
|
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Not Applicable
{| class="wikitable sortable"
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!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
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==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>
There are multiple genes with single nucleotide variations that have been reported only in metastatic solitary fibrous tumor tissues including TP53 and APAF1.<ref name=":1">{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019|title=Molecular changes in solitary fibrous tumor progression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746689/|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=0946-2716|pmc=6746689|pmid=31321477}}</ref>
{| 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>''EGFR''
|''TERT''
 
|Promoter mutations
<br />
|Oncogene
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Common<ref name=":3">{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M|last5=Patton|first5=Kurt T|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://linkinghub.elsevier.com/retrieve/pii/S0893395222023328|journal=Modern Pathology|language=en|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126}}</ref><ref>{{Cite journal|last=Liu|first=Xiaoli|last2=Bishop|first2=Justin|last3=Shan|first3=Yuan|last4=Pai|first4=Sara|last5=Liu|first5=Dingxie|last6=Murugan|first6=Avaniyapuram Kannan|last7=Sun|first7=Hui|last8=El-Naggar|first8=Adel K|last9=Xing|first9=Mingzhao|date=2013-08|title=Highly prevalent TERT promoter mutations in aggressive thyroid cancers|url=https://erc.bioscientifica.com/view/journals/erc/20/4/603.xml|journal=Endocrine-Related Cancer|volume=20|issue=4|pages=603–610|doi=10.1530/ERC-13-0210|issn=1351-0088|pmc=PMC3782569|pmid=23766237}}</ref><ref>{{Cite journal|last=Killela|first=Patrick J.|last2=Reitman|first2=Zachary J.|last3=Jiao|first3=Yuchen|last4=Bettegowda|first4=Chetan|last5=Agrawal|first5=Nishant|last6=Diaz|first6=Luis A.|last7=Friedman|first7=Allan H.|last8=Friedman|first8=Henry|last9=Gallia|first9=Gary L.|date=2013-04-09|title=TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal|url=https://pnas.org/doi/full/10.1073/pnas.1303607110|journal=Proceedings of the National Academy of Sciences|language=en|volume=110|issue=15|pages=6021–6026|doi=10.1073/pnas.1303607110|issn=0027-8424|pmc=PMC3625331|pmid=23530248}}</ref><ref>{{Cite journal|last=Koelsche|first=Christian|last2=Renner|first2=Marcus|last3=Hartmann|first3=Wolfgang|last4=Brandt|first4=Regine|last5=Lehner|first5=Burkhard|last6=Waldburger|first6=Nina|last7=Alldinger|first7=Ingo|last8=Schmitt|first8=Thomas|last9=Egerer|first9=Gerlinde|date=2014-12|title=TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities|url=https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-33-33|journal=Journal of Experimental & Clinical Cancer Research|language=en|volume=33|issue=1|doi=10.1186/1756-9966-33-33|issn=1756-9966}}</ref><ref name=":2">{{Cite journal|last=Demicco|first=Elizabeth G.|last2=Wani|first2=Khalida|last3=Ingram|first3=Davis|last4=Wagner|first4=Michael|last5=Maki|first5=Robert G.|last6=Rizzo|first6=Anthony|last7=Meeker|first7=Alan|last8=Lazar|first8=Alexander J.|last9=Wang|first9=Wei-Lien|date=2018-11|title=TERT promoter mutations in solitary fibrous tumour|url=https://pubmed.ncbi.nlm.nih.gov/29985536|journal=Histopathology|volume=73|issue=5|pages=843–851|doi=10.1111/his.13703|issn=1365-2559|pmid=29985536}}</ref>
|<span class="blue-text">EXAMPLE:</span> Oncogene
|P<ref name=":0" /><ref name=":3" /><ref name=":2" /><ref>{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019-10|title=Molecular changes in solitary fibrous tumor progression|url=https://pubmed.ncbi.nlm.nih.gov/31321477|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=1432-1440|pmc=6746689|pmid=31321477}}</ref><ref>{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M.|last5=Patton|first5=Kurt T.|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D.|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://pubmed.ncbi.nlm.nih.gov/27562490|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126|issn=1530-0285|pmc=5731237|pmid=27562490}}</ref>
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|No
|<span class="blue-text">EXAMPLE:</span> T
|
|<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
|''TP53''
<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|Deletions or mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|Common<ref name=":4">{{Cite journal|last=Yao|first=Chen-Chen|last2=Zhou|first2=Jian|last3=Li|first3=Xiao|last4=Yang|first4=Jun|last5=Chen|first5=Gang|last6=Wei|first6=Jia|last7=Fan|first7=Qin-He|last8=Gong|first8=Qi-Xing|date=2023|title=Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases|url=https://pubmed.ncbi.nlm.nih.gov/38239634|journal=Frontiers in Oncology|volume=13|pages=1272090|doi=10.3389/fonc.2023.1272090|issn=2234-943X|pmc=PMC10796168|pmid=38239634}}</ref><ref name=":1" />
|<span class="blue-text">EXAMPLE:</span> P
|P<ref>{{Cite journal|last=Machado|first=Isidro|last2=Morales|first2=Gema Nieto|last3=Cruz|first3=Julia|last4=Lavernia|first4=Javier|last5=Giner|first5=Francisco|last6=Navarro|first6=Samuel|last7=Ferrandez|first7=Antonio|last8=Llombart-Bosch|first8=Antonio|date=2020-04|title=Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification|url=https://pubmed.ncbi.nlm.nih.gov/31529158|journal=Virchows Archiv: An International Journal of Pathology|volume=476|issue=4|pages=597–607|doi=10.1007/s00428-019-02660-3|issn=1432-2307|pmid=31529158}}</ref><ref name=":4" />
|
|No
|<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.
|Single base pair substitution have been identified in exon 5 or exon 6 of TP53. <ref name=":3" /> Mutations of TP53 have been associated with malignant and dedifferentiated SFTs.<ref>{{Cite journal|last=Dagrada|first=Gian P.|last2=Spagnuolo|first2=Rosalin D.|last3=Mauro|first3=Valentina|last4=Tamborini|first4=Elena|last5=Cesana|first5=Luca|last6=Gronchi|first6=Alessandro|last7=Stacchiotti|first7=Silvia|last8=Pierotti|first8=Marco A.|last9=Negri|first9=Tiziana|date=2015-08|title=Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation|url=https://pubmed.ncbi.nlm.nih.gov/26022454|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=28|issue=8|pages=1074–1083|doi=10.1038/modpathol.2015.70|issn=1530-0285|pmid=26022454}}</ref><ref>{{Cite journal|last=Kurisaki-Arakawa|first=Aiko|last2=Akaike|first2=Keisuke|last3=Hara|first3=Kieko|last4=Arakawa|first4=Atsushi|last5=Takahashi|first5=Michiko|last6=Mitani|first6=Keiko|last7=Yao|first7=Takashi|last8=Saito|first8=Tsuyoshi|date=2014-11|title=A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation|url=https://pubmed.ncbi.nlm.nih.gov/25015562|journal=Virchows Archiv: An International Journal of Pathology|volume=465|issue=5|pages=615–621|doi=10.1007/s00428-014-1625-3|issn=1432-2307|pmid=25015562}}</ref><ref>{{Cite journal|last=Nonaka|first=Haruna|last2=Kandori|first2=Shuya|last3=Nitta|first3=Satoshi|last4=Shiga|first4=Masanobu|last5=Nagumo|first5=Yoshiyuki|last6=Kimura|first6=Tomokazu|last7=Kawahara|first7=Takashi|last8=Negoro|first8=Hiromitsu|last9=Hoshi|first9=Akio|date=2021|title=Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study|url=https://pubmed.ncbi.nlm.nih.gov/35004271|journal=Frontiers in Oncology|volume=11|pages=736969|doi=10.3389/fonc.2021.736969|issn=2234-943X|pmc=8727594|pmid=35004271}}</ref>
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|''ARAF1''
|<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
|
|
|
|Other
|Common
|P<ref name=":1" />
|No
|Alteration of APAF1 results in gain of a stop codon. The gene is inactivated by DNA methylation of the promoter region. Decreased APAF1 is considered to lead to inhibition of apoptosis.  This alteration and decreased APAF1 mRNA expression was observed in metastatic SFT.
|-
|-
|
|
Line 308: Line 136:
|
|
|}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.
There are multiple genes with single nucleotide variations that have been reported only in metastatic solitary fibrous tumor tissues including TP53 and APAF1.<ref name=":1">{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019|title=Molecular changes in solitary fibrous tumor progression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746689/|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=0946-2716|pmc=6746689|pmid=31321477}}</ref>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|TERT
|Oncogene
|13-29% <ref name=":3">{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M|last5=Patton|first5=Kurt T|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://linkinghub.elsevier.com/retrieve/pii/S0893395222023328|journal=Modern Pathology|language=en|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126}}</ref><ref>{{Cite journal|last=Liu|first=Xiaoli|last2=Bishop|first2=Justin|last3=Shan|first3=Yuan|last4=Pai|first4=Sara|last5=Liu|first5=Dingxie|last6=Murugan|first6=Avaniyapuram Kannan|last7=Sun|first7=Hui|last8=El-Naggar|first8=Adel K|last9=Xing|first9=Mingzhao|date=2013-08|title=Highly prevalent TERT promoter mutations in aggressive thyroid cancers|url=https://erc.bioscientifica.com/view/journals/erc/20/4/603.xml|journal=Endocrine-Related Cancer|volume=20|issue=4|pages=603–610|doi=10.1530/ERC-13-0210|issn=1351-0088|pmc=PMC3782569|pmid=23766237}}</ref><ref>{{Cite journal|last=Killela|first=Patrick J.|last2=Reitman|first2=Zachary J.|last3=Jiao|first3=Yuchen|last4=Bettegowda|first4=Chetan|last5=Agrawal|first5=Nishant|last6=Diaz|first6=Luis A.|last7=Friedman|first7=Allan H.|last8=Friedman|first8=Henry|last9=Gallia|first9=Gary L.|date=2013-04-09|title=TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal|url=https://pnas.org/doi/full/10.1073/pnas.1303607110|journal=Proceedings of the National Academy of Sciences|language=en|volume=110|issue=15|pages=6021–6026|doi=10.1073/pnas.1303607110|issn=0027-8424|pmc=PMC3625331|pmid=23530248}}</ref><ref>{{Cite journal|last=Koelsche|first=Christian|last2=Renner|first2=Marcus|last3=Hartmann|first3=Wolfgang|last4=Brandt|first4=Regine|last5=Lehner|first5=Burkhard|last6=Waldburger|first6=Nina|last7=Alldinger|first7=Ingo|last8=Schmitt|first8=Thomas|last9=Egerer|first9=Gerlinde|date=2014-12|title=TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities|url=https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-33-33|journal=Journal of Experimental & Clinical Cancer Research|language=en|volume=33|issue=1|doi=10.1186/1756-9966-33-33|issn=1756-9966}}</ref><ref name=":2">{{Cite journal|last=Demicco|first=Elizabeth G.|last2=Wani|first2=Khalida|last3=Ingram|first3=Davis|last4=Wagner|first4=Michael|last5=Maki|first5=Robert G.|last6=Rizzo|first6=Anthony|last7=Meeker|first7=Alan|last8=Lazar|first8=Alexander J.|last9=Wang|first9=Wei-Lien|date=2018-11|title=TERT promoter mutations in solitary fibrous tumour|url=https://pubmed.ncbi.nlm.nih.gov/29985536|journal=Histopathology|volume=73|issue=5|pages=843–851|doi=10.1111/his.13703|issn=1365-2559|pmid=29985536}}</ref>
|
|
|No
|Yes<ref name=":0" /><ref name=":3" /><ref name=":2" /><ref>{{Cite journal|last=Park|first=Hyung Kyu|last2=Yu|first2=Dan Bi|last3=Sung|first3=Minjung|last4=Oh|first4=Ensel|last5=Kim|first5=Mingi|last6=Song|first6=Ji-Young|last7=Lee|first7=Mi-Sook|last8=Jung|first8=Kyungsoo|last9=Noh|first9=Ka-Won|date=2019-10|title=Molecular changes in solitary fibrous tumor progression|url=https://pubmed.ncbi.nlm.nih.gov/31321477|journal=Journal of Molecular Medicine (Berlin, Germany)|volume=97|issue=10|pages=1413–1425|doi=10.1007/s00109-019-01815-8|issn=1432-1440|pmc=6746689|pmid=31321477}}</ref><ref>{{Cite journal|last=Bahrami|first=Armita|last2=Lee|first2=Seungjae|last3=Schaefer|first3=Inga-Marie|last4=Boland|first4=Jennifer M.|last5=Patton|first5=Kurt T.|last6=Pounds|first6=Stanley|last7=Fletcher|first7=Christopher D.|date=2016-12|title=TERT promoter mutations and prognosis in solitary fibrous tumor|url=https://pubmed.ncbi.nlm.nih.gov/27562490|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=12|pages=1511–1522|doi=10.1038/modpathol.2016.126|issn=1530-0285|pmc=5731237|pmid=27562490}}</ref>
|No
|
|-
|TP53
|TSG
|6.3-41%<ref name=":4">{{Cite journal|last=Yao|first=Chen-Chen|last2=Zhou|first2=Jian|last3=Li|first3=Xiao|last4=Yang|first4=Jun|last5=Chen|first5=Gang|last6=Wei|first6=Jia|last7=Fan|first7=Qin-He|last8=Gong|first8=Qi-Xing|date=2023|title=Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases|url=https://pubmed.ncbi.nlm.nih.gov/38239634|journal=Frontiers in Oncology|volume=13|pages=1272090|doi=10.3389/fonc.2023.1272090|issn=2234-943X|pmc=PMC10796168|pmid=38239634}}</ref><ref name=":1" />
|
|
|No
|Yes<ref>{{Cite journal|last=Machado|first=Isidro|last2=Morales|first2=Gema Nieto|last3=Cruz|first3=Julia|last4=Lavernia|first4=Javier|last5=Giner|first5=Francisco|last6=Navarro|first6=Samuel|last7=Ferrandez|first7=Antonio|last8=Llombart-Bosch|first8=Antonio|date=2020-04|title=Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification|url=https://pubmed.ncbi.nlm.nih.gov/31529158|journal=Virchows Archiv: An International Journal of Pathology|volume=476|issue=4|pages=597–607|doi=10.1007/s00428-019-02660-3|issn=1432-2307|pmid=31529158}}</ref><ref name=":4" />
|No
|Single base pair substitution have been identified in exon 5 or exon 6 of TP53. <ref name=":3" /> Mutations of TP53 have been associated with malignant and dedifferentiated SFTs.<ref>{{Cite journal|last=Dagrada|first=Gian P.|last2=Spagnuolo|first2=Rosalin D.|last3=Mauro|first3=Valentina|last4=Tamborini|first4=Elena|last5=Cesana|first5=Luca|last6=Gronchi|first6=Alessandro|last7=Stacchiotti|first7=Silvia|last8=Pierotti|first8=Marco A.|last9=Negri|first9=Tiziana|date=2015-08|title=Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation|url=https://pubmed.ncbi.nlm.nih.gov/26022454|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=28|issue=8|pages=1074–1083|doi=10.1038/modpathol.2015.70|issn=1530-0285|pmid=26022454}}</ref><ref>{{Cite journal|last=Kurisaki-Arakawa|first=Aiko|last2=Akaike|first2=Keisuke|last3=Hara|first3=Kieko|last4=Arakawa|first4=Atsushi|last5=Takahashi|first5=Michiko|last6=Mitani|first6=Keiko|last7=Yao|first7=Takashi|last8=Saito|first8=Tsuyoshi|date=2014-11|title=A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation|url=https://pubmed.ncbi.nlm.nih.gov/25015562|journal=Virchows Archiv: An International Journal of Pathology|volume=465|issue=5|pages=615–621|doi=10.1007/s00428-014-1625-3|issn=1432-2307|pmid=25015562}}</ref><ref>{{Cite journal|last=Nonaka|first=Haruna|last2=Kandori|first2=Shuya|last3=Nitta|first3=Satoshi|last4=Shiga|first4=Masanobu|last5=Nagumo|first5=Yoshiyuki|last6=Kimura|first6=Tomokazu|last7=Kawahara|first7=Takashi|last8=Negoro|first8=Hiromitsu|last9=Hoshi|first9=Akio|date=2021|title=Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study|url=https://pubmed.ncbi.nlm.nih.gov/35004271|journal=Frontiers in Oncology|volume=11|pages=736969|doi=10.3389/fonc.2021.736969|issn=2234-943X|pmc=8727594|pmid=35004271}}</ref>
|-
|APAF1
|Other
|66.7%
|
|
|No
|Yes<ref name=":1" />
|No
|Alteration of APAF1 results in gain of a stop codon. The gene is inactivated by DNA methylation of the promoter region. Decreased APAF1 is considered to lead to inhibition of apoptosis.  This alteration and decreased APAF1 mRNA expression was observed in metastatic SFT.
|}


==Epigenomic Alterations==
==Epigenomic Alterations==
Not Applicable
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"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> 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
|-
|
|
|
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 387: Line 149:
|}
|}


==Genetic Diagnostic Testing Methods==
# Fusion testing
#* Next generation sequencing (NGS) using mRNA to detect the ''NAB2::STAT6'' fusion
#* Breakpoint fluorescence in situ hybridization (FISH) probe for ''STAT6''
#* Dual color dual fusion probe targeting both genes<ref>{{Cite journal|last=Kouba|first=Erik|last2=Simper|first2=Novae B.|last3=Chen|first3=Shaoxiong|last4=Williamson|first4=Sean R.|last5=Grignon|first5=David J.|last6=Eble|first6=John N.|last7=MacLennan|first7=Gregory T.|last8=Montironi|first8=Rodolfo|last9=Lopez-Beltran|first9=Antonio|date=2017-06-01|title=Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene|url=https://jcp.bmj.com/content/70/6/508|journal=Journal of Clinical Pathology|language=en|volume=70|issue=6|pages=508–514|doi=10.1136/jclinpath-2016-204088|issn=0021-9746|pmid=27802414}}</ref>
#** a direct confirmation for ''NAB2::STAT6'' fusion
#* Immunohistochemistry testing, STAT6 (signal transducer and activator of transcription 6) immunostain
#** nuclear staining
#** high sensitivity and specificity


==Genetic Diagnostic Testing Methods==
Ancillary studies such as immunohistochemistry and molecular tests are useful in differentiating soft tissue tumors. SFTs have historically been diagnosed by morphology and strong diffuse CD34 positivity. Additional immunohistochemical phenotype previously used for identification included expression of Bcl2, CD99, and vimentin and absence of expression of epithelial, muscle, and neural markers. However, the introduction of STAT6 (signal transducer and activator of transcription 6) immunostain now dominates due to its high sensitivity and specificity. STAT6 expression is demonstrated by nuclear staining. Next generation sequencing (NGS) using mRNA is also highly useful in detecting the NAB2::STAT6 fusion. Breakapart fluorescence in situ hybridization (FISH) probe for STAT6 can detect rearrangement of this gene.  In the context of SFT, the rearrangement of the ''STAT6'' gene is highly suggestive for the presence of ''NAB2-STAT6'' fusion. [https://pubmed.ncbi.nlm.nih.gov/27802414/ A dual color dual fusion probe targeting both genes would be a direct confirmation for ''NAB2-STAT6'' fusion.]
==Familial Forms==
==Familial Forms==
Not Applicable
Not Applicable
==Additional Information==
==Additional Information==


This disease is <u>defined/characterized</u> as detailed below:
None
 
*Solitary fibrous tumor (SFT) is a mesenchymal spindle cell neoplasm that can develop at any site in the body, including soft tissue, visceral organs, bone, etc.  It was first described by Klemperer and Rabin<ref>{{Cite journal|last=Klemperer|first=Paul|last2=Rabin|first2=Coleman B.|date=1992-01|title=Primary Neoplasms of the pleura. A report of five cases|url=https://onlinelibrary.wiley.com/doi/10.1002/ajim.4700220103|journal=American Journal of Industrial Medicine|language=en|volume=22|issue=1|pages=4–31|doi=10.1002/ajim.4700220103|issn=0271-3586}}</ref> in 1992 as a tumor of the pleura. However, since then this entity has been increasingly described from extrapleural sites. A morphologic clue to the diagnosis is the distinctive branching “staghorn” vessels. SFT is characterized by ''NAB2::STAT6'' fusion resulting from a small paracentric inversion at chromosome 12q13.
 
The <u>epidemiology/prevalence</u> of this disease is detailed below:
 
*SFT occurs most commonly in adults with no gender predilection. Incidence of the tumor is highest in the age group of 40-70 years.
 
The <u>clinical features</u> of this disease are detailed below:
 
Signs and symptoms - SFTs present as slow-growing, painless neoplasms. Clinical symptoms can be due to mass effect in the site of involvement. e.g. Abdomen/Pelvis: abdominal distention, constipation, urinary retention Head/Neck: Dysphonia, nasal obstruction, dysphagia
 
Laboratory findings - N/A
 
The <u>sites of involvement</u> of this disease are detailed below:
 
*SFTs may occur at any site of the body. Involvement of head and neck, deep soft tissues, abdominal cavity, retroperitoneum, pelvis, bone, and visceral organs have been reported.
 
The <u>morphologic features</u> of this disease are detailed below:
 
*Morphologically, biopsy or resection specimens will show a bland spindle cell proliferation arranged haphazardly in a background of collagenous stroma. Cells contain ovoid nuclei within eosinophilic cytoplasm with indistinct cell borders. Tumors can vary in cellularity and stromal collagen. On low power, branching, “staghorn” shaped vessels can often be appreciated. Mitotic counts are usually low. Myxoid and lipomatous change have been described. SFT with adipocytic component are referred to as fat-forming (lipomatous) SFTs. There is also a variant known as giant cell rich SFT, which has the classic patternless spindle cell proliferation admixed with multinucleated giant cells. Dedifferentiated SFTs will show conventional SFT transitioning to a high-grade pleomorphic variant. Heterologous elements may be present. Standard immunophenotypic expression of CD34 and STAT6 is often lost in the dedifferentiated component.
 
The <u>immunophenotype</u> of this disease is detailed below:
 
Positive - CD34, STAT6 (nuclear), BCL2 (30%), CD99 (70%), EMA (30%) and Actin (20%)<ref name=":5">Goldblum, John R, et al. ''Enzinger & Weiss’s Soft Tissue Tumors''. 7th ed., Philadelphia, PA, Elsevier, 2020, pp. 1133–1147.</ref>
 
Negative - S100, Desmin and Cytokeratins<ref name=":5" />


==Links==
==Links==
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the 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 on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span>
<references />
 
==Notes==
==Notes==


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

Revision as of 12:04, 23 November 2025


Soft Tissue and Bone Tumours (Who Classification, 5th ed.)

Primary Author(s)*

Reba Daniel and Shashi Shetty

WHO Classification of Disease

Structure Disease
Book Soft Tissue and Bone Tumours (5th ed.)
Category Soft tissue tumours
Family Fibroblastic and myofibroblastic tumours
Type Solitary fibrous tumour
Subtype(s) N/A

Related Terminology

Acceptable N/A
Not Recommended Solitary fibrous tumour / Haemangiopericytoma; Haemangiopericytoma

Gene Rearrangements

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
N/A NAB2-STAT6 Paracentric inversion results in the fusion.[1][2][3][4][5][6] The fusion is thought to convert wildtype NAB2 from a transcriptional repressor of EGR1-mediated signalling into a transcriptional activator via replacement of the C-terminal repression domain by the transcriptional activation domain of STAT6, thereby resulting in a feedforward loop of constitutive EGR1-mediated transactivation of proliferation and survival-associated growth factors, including IGF2 and FGFR1. [3] inv(12)(q13q13) Common D Y (WHO) NAB2-STAT6 gene fusions are pathognomonic for SFT. Many different breakpoints in the exons and introns are associated with this fusion. Ex: NAB2ex4-STAT6ex2; NAB2ex6-STAT6ex16/17.

Individual Region Genomic Gain/Loss/LOH

None

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A N/A N/A N/A N/A N/A N/A

Characteristic Chromosomal or Other Global Mutational Patterns

None

Chromosomal Pattern Molecular Pathogenesis 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
N/A N/A N/A N/A N/A N/A

Gene Mutations (SNV/INDEL)

There are multiple genes with single nucleotide variations that have been reported only in metastatic solitary fibrous tumor tissues including TP53 and APAF1.[7]

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other 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
TERT Promoter mutations Oncogene Common[8][9][10][11][12] P[6][8][12][13][14] No
TP53


Deletions or mutations Tumor Supressor Gene Common[15][7] P[16][15] No Single base pair substitution have been identified in exon 5 or exon 6 of TP53. [8] Mutations of TP53 have been associated with malignant and dedifferentiated SFTs.[17][18][19]
ARAF1 Other Common P[7] No Alteration of APAF1 results in gain of a stop codon. The gene is inactivated by DNA methylation of the promoter region. Decreased APAF1 is considered to lead to inhibition of apoptosis. This alteration and decreased APAF1 mRNA expression was observed in metastatic SFT.

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

None

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
NAB2::STAT6; Activating mutation EGR Pathway Increased activation of EGR1

Genetic Diagnostic Testing Methods

  1. Fusion testing
    • Next generation sequencing (NGS) using mRNA to detect the NAB2::STAT6 fusion
    • Breakpoint fluorescence in situ hybridization (FISH) probe for STAT6
    • Dual color dual fusion probe targeting both genes[20]
      • a direct confirmation for NAB2::STAT6 fusion
    • Immunohistochemistry testing, STAT6 (signal transducer and activator of transcription 6) immunostain
      • nuclear staining
      • high sensitivity and specificity

Familial Forms

Not Applicable

Additional Information

None

Links

None

References

  1. ↑ Chmielecki, Juliann; et al. (2013-02). "Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors". Nature Genetics. 45 (2): 131–132. doi:10.1038/ng.2522. ISSN 1061-4036. Check date values in: |date= (help)
  2. ↑ Mohajeri, Arezoo; et al. (2013-10). "Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor". Genes, Chromosomes and Cancer. 52 (10): 873–886. doi:10.1002/gcc.22083. ISSN 1045-2257. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 Robinson, Dan R; et al. (2013-02). "Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing". Nature Genetics. 45 (2): 180–185. doi:10.1038/ng.2509. ISSN 1061-4036. Check date values in: |date= (help)
  4. ↑ Huang, Shih‐Chiang; et al. (2016-02). "The clinicopathological significance of NAB 2‐ STAT 6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors". Cancer Medicine. 5 (2): 159–168. doi:10.1002/cam4.572. ISSN 2045-7634. Check date values in: |date= (help)
  5. ↑ Vogels, Rob JC; et al. (2014-12). "Solitary fibrous tumor – clinicopathologic, immunohistochemical and molecular analysis of 28 cases". Diagnostic Pathology. 9 (1). doi:10.1186/s13000-014-0224-6. ISSN 1746-1596. Check date values in: |date= (help)
  6. ↑ 6.0 6.1 Akaike, Keisuke; et al. (2015-03). "Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential". Human Pathology. 46 (3): 347–356. doi:10.1016/j.humpath.2014.11.018. Check date values in: |date= (help)
  7. ↑ 7.0 7.1 7.2 Park, Hyung Kyu; et al. (2019). "Molecular changes in solitary fibrous tumor progression". Journal of Molecular Medicine (Berlin, Germany). 97 (10): 1413–1425. doi:10.1007/s00109-019-01815-8. ISSN 0946-2716. PMC 6746689. PMID 31321477.
  8. ↑ 8.0 8.1 8.2 Bahrami, Armita; et al. (2016-12). "TERT promoter mutations and prognosis in solitary fibrous tumor". Modern Pathology. 29 (12): 1511–1522. doi:10.1038/modpathol.2016.126. Check date values in: |date= (help)
  9. ↑ Liu, Xiaoli; et al. (2013-08). "Highly prevalent TERT promoter mutations in aggressive thyroid cancers". Endocrine-Related Cancer. 20 (4): 603–610. doi:10.1530/ERC-13-0210. ISSN 1351-0088. PMC 3782569. PMID 23766237. Check date values in: |date= (help)CS1 maint: PMC format (link)
  10. ↑ Killela, Patrick J.; et al. (2013-04-09). "TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal". Proceedings of the National Academy of Sciences. 110 (15): 6021–6026. doi:10.1073/pnas.1303607110. ISSN 0027-8424. PMC 3625331. PMID 23530248.CS1 maint: PMC format (link)
  11. ↑ Koelsche, Christian; et al. (2014-12). "TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities". Journal of Experimental & Clinical Cancer Research. 33 (1). doi:10.1186/1756-9966-33-33. ISSN 1756-9966. Check date values in: |date= (help)
  12. ↑ 12.0 12.1 Demicco, Elizabeth G.; et al. (2018-11). "TERT promoter mutations in solitary fibrous tumour". Histopathology. 73 (5): 843–851. doi:10.1111/his.13703. ISSN 1365-2559. PMID 29985536. Check date values in: |date= (help)
  13. ↑ Park, Hyung Kyu; et al. (2019-10). "Molecular changes in solitary fibrous tumor progression". Journal of Molecular Medicine (Berlin, Germany). 97 (10): 1413–1425. doi:10.1007/s00109-019-01815-8. ISSN 1432-1440. PMC 6746689. PMID 31321477. Check date values in: |date= (help)
  14. ↑ Bahrami, Armita; et al. (2016-12). "TERT promoter mutations and prognosis in solitary fibrous tumor". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 29 (12): 1511–1522. doi:10.1038/modpathol.2016.126. ISSN 1530-0285. PMC 5731237. PMID 27562490. Check date values in: |date= (help)
  15. ↑ 15.0 15.1 Yao, Chen-Chen; et al. (2023). "Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases". Frontiers in Oncology. 13: 1272090. doi:10.3389/fonc.2023.1272090. ISSN 2234-943X. PMC PMC10796168 Check |pmc= value (help). PMID 38239634 Check |pmid= value (help).CS1 maint: PMC format (link)
  16. ↑ Machado, Isidro; et al. (2020-04). "Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification". Virchows Archiv: An International Journal of Pathology. 476 (4): 597–607. doi:10.1007/s00428-019-02660-3. ISSN 1432-2307. PMID 31529158. Check date values in: |date= (help)
  17. ↑ Dagrada, Gian P.; et al. (2015-08). "Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 28 (8): 1074–1083. doi:10.1038/modpathol.2015.70. ISSN 1530-0285. PMID 26022454. Check date values in: |date= (help)
  18. ↑ Kurisaki-Arakawa, Aiko; et al. (2014-11). "A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation". Virchows Archiv: An International Journal of Pathology. 465 (5): 615–621. doi:10.1007/s00428-014-1625-3. ISSN 1432-2307. PMID 25015562. Check date values in: |date= (help)
  19. ↑ Nonaka, Haruna; et al. (2021). "Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study". Frontiers in Oncology. 11: 736969. doi:10.3389/fonc.2021.736969. ISSN 2234-943X. PMC 8727594 Check |pmc= value (help). PMID 35004271 Check |pmid= value (help).
  20. ↑ Kouba, Erik; et al. (2017-06-01). "Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene". Journal of Clinical Pathology. 70 (6): 508–514. doi:10.1136/jclinpath-2016-204088. ISSN 0021-9746. PMID 27802414.

Notes

*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 Associate Editor 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): *Citation of this Page: “Solitary fibrous tumour”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/23/2025, https://ccga.io/index.php/STBT5:Solitary fibrous tumour.

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