Compendium of Cancer Genome Aberrations

STBT5:Solitary fibrous tumour: Difference between revisions

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<span style="color:#0070C0"> (''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], 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 to a table, click nearby within the table and select the > symbol that appears to be given options. 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>
{{DISPLAYTITLE:Solitary fibrous tumour}}
 
[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]
==Primary Author(s)*==
==Primary Author(s)*==
Reba Daniel and Shashi Shetty
Yiting Li MD, Reba Daniel MD, and Shashi Shetty PhD
==WHO Classification of Disease==
==WHO Classification of Disease==
{| class="wikitable"
{| class="wikitable"
!Structure
!Structure
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|-
|-
|Book
|Book
|[https://tumourclassification.iarc.who.int/home WHO Classification of Soft Tissue and Bone Tumours (5th Edition)]
|Soft Tissue and Bone Tumours (5th ed.)
|-
|-
|Category
|Category
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|-
|-
|Subtype(s)
|Subtype(s)
|None
|N/A
|}
|}
==Definition / Description of Disease==
==Related Terminology==
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.
 
==Synonyms / Terminology==
Formerly SFTs were categorized as hemangiopericytomas.
==Epidemiology / Prevalence==
SFT occurs most commonly in adults with no gender predilection. Incidence of the tumor is highest in the age group of 40-70 years.
==Clinical Features==
<br />
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|SFTs present as slow-growing, painless neoplasms. Clinical symptoms can be due to mass effect in the site of involvement.
|Acceptable
e.g. Abdomen/Pelvis: abdominal distention, constipation, urinary retention
|N/A
 
Head/Neck: Dysphonia, nasal obstruction, dysphagia
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|
|Haemangiopericytoma; Giant cell angiofibroma; Benign solitary fibrous tumour
|}
|}
==Sites of Involvement==
 
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.
==Gene Rearrangements==
==Morphologic Features==
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.
==Immunophenotype<ref>Goldblum, John R, et al. ''Enzinger & Weiss’s Soft Tissue Tumors''. 7th ed., Philadelphia, PA, Elsevier, 2020, pp. 1133–1147.</ref>==
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"
|-
!Finding!!Marker
|-
|Positive||CD34
|-
|Positive||STAT6 (nuclear)
|-
|Positive||BCL2 (30%)
|-
|Positive||CD99 (70%)
|-
|Positive
|EMA (30%)
|-
|Positive
|Actin (20%)
|-
|Negative
|S100
|-
|Negative
|Desmin
|-
|Negative
|Cytokeratins
|}
==Chromosomal Rearrangements (Gene Fusions)==
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"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Diagnostic Significance (Yes, No or Unknown)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other 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%
|''NAB2''
|Yes
|''STAT6''
|Unknown
|This fusion is caused by a paracentric inversion on chromosome 12q and encodes a chimeric protein that combines the EGR-binding domain of NAB2 with the transactivation domain of STAT6, thereby results in a feedforward loop of constitutive EGR1-mediated transactivation of proliferation and survival-associated growth factors.<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 name=":4">{{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>  
|No
|inv(12)(q13q13)
|Many different breakpoints in the exons and introns are associated with this fusion. Ex: ''NAB2''ex4-''STAT6''ex2; ''NAB2''ex6-''STAT6''ex16/17
|Common
|D
|Yes (WHO)
|''NAB2''::''STAT6'' gene fusions are pathognomonic for SFT. Many different breakpoints in the exons and introns are associated with this fusion. The most common fusion variants: ''NAB2''ex4::''STAT6''ex2; ''NAB2''ex6::''STAT6''ex16/17. <ref name=":4" /><ref name=":5" /> Antiangiogenic therapy showed activity in advanced and progressive SFT<ref>{{Cite journal|last=de Bernardi|first=Axel|last2=Dufresne|first2=Armelle|last3=Mishellany|first3=Florence|last4=Blay|first4=Jean-Yves|last5=Ray-Coquard|first5=Isabelle|last6=Brahmi|first6=Mehdi|date=2022-02-20|title=Novel Therapeutic Options for Solitary Fibrous Tumor: Antiangiogenic Therapy and Beyond|url=https://www.mdpi.com/2072-6694/14/4/1064|journal=Cancers|language=en|volume=14|issue=4|pages=1064|doi=10.3390/cancers14041064|issn=2072-6694}}</ref>
|}
|}
==Individual Region Genomic Gain / Loss / LOH==


 
==Individual Region Genomic Gain/Loss/LOH==
Not Applicable
None
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|
|
|
|
|
|
|
|
|-
|-
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|}
|}
==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
 
None
Not Applicable
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!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)==
==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.<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>  
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"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!'''Diagnostic Significance (Yes, No or Unknown)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|TERT
|''TERT''
|Promoter mutations
|Oncogene
|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>
|Common
|
|P
|
|No
|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>
|''TERT'' promoter mutations were more frequent in tumors with higher risk of metastasis, have a significant association with malignant SFTs, and may identify intermediate-risk tumors with poorer prognosis.<ref name=":0" /><ref name=":1" /><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=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><ref name=":6">{{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=2024-01-04|title=Prognostic analysis of extrameningeal solitary fibrous tumor using the modified Demicco model: a clinicopathologic study of 111 Chinese cases|url=https://www.frontiersin.org/articles/10.3389/fonc.2023.1272090/full|journal=Frontiers in Oncology|volume=13|doi=10.3389/fonc.2023.1272090|issn=2234-943X}}</ref><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=http://link.springer.com/10.1007/s00428-019-02660-3|journal=Virchows Archiv|language=en|volume=476|issue=4|pages=597–607|doi=10.1007/s00428-019-02660-3|issn=0945-6317}}</ref>
|No
|
|-
|-
|TP53
|''TP53''
|TSG
<br />
|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" />
|Missense or frameshift mutation<ref name=":3" />
|
|Tumor Supressor Gene
|
|Common
|No
|P
|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
|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>
|Mutations of ''TP53'' have been associated with malignant and dedifferentiated SFTs.<ref name=":0" /><ref name=":6" /><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://linkinghub.elsevier.com/retrieve/pii/S0893395222013904|journal=Modern Pathology|language=en|volume=28|issue=8|pages=1074–1083|doi=10.1038/modpathol.2015.70}}</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
|''APAF1''
|LOF mutation<ref name=":1" />
|Other
|Other
|66.7%
|Common
|
|P
|
|No
|No
|Yes<ref name=":1" />
|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.<ref name=":1" />
|No
|}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.
|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==
{| class="wikitable sortable"
{| class="wikitable sortable"
Line 183: Line 134:
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|NAB2::STAT6; Activating mutation
|''NAB2::STAT6''; Activating mutation
|EGR Pathway
|EGR Pathway
|Increased activation of EGR1
|Increased activation of EGR1
|}
|}
==Genetic Diagnostic Testing Methods==
==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.]
 
# '''Fusion testing'''
#* Next generation sequencing (NGS) using mRNA targeting the fusion
#* Dual color dual fusion fluorescence ''in situ'' hybridization (FISH) 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
# '''Breakpoint detection'''
#* Breakpoint fluorescence ''in situ'' hybridization (FISH) probe for ''STAT6''
 
==Familial Forms==
==Familial Forms==
Not Applicable
Not Applicable
==Additional Information==
==Additional Information==
Put your text here
 
'''Immunohistochemistry testing'''
* STAT6 (signal transducer and activator of transcription 6) immunostain
** nuclear staining
** high sensitivity and specificity<ref>{{Cite journal|last=Doyle|first=Leona A|last2=Vivero|first2=Marina|last3=Fletcher|first3=Christopher DM|last4=Mertens|first4=Fredrik|last5=Hornick|first5=Jason L|date=2014-03|title=Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics|url=https://linkinghub.elsevier.com/retrieve/pii/S0893395222018294|journal=Modern Pathology|language=en|volume=27|issue=3|pages=390–395|doi=10.1038/modpathol.2013.164}}</ref>
==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==
<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 CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
 
<references />
 
<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): *''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:DISEASE]]
[[Category:Diseases S]]
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