Compendium of Cancer Genome Aberrations

STBT5:Myxoinflammatory fibroblastic sarcoma: Difference between revisions

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{{DISPLAYTITLE:Myxoinflammatory fibroblastic sarcoma}}
{{DISPLAYTITLE:Myxoinflammatory fibroblastic sarcoma}}
[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]
[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]
==Primary Author(s)*==
Mokhtar H. Abdelhammed, MD; Kathleen Schieffer, PhD


{{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)*==
Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
==WHO Classification of Disease==
==WHO Classification of Disease==


Line 41: Line 38:


==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>
''BRAF'' gene fusions are identified in approximately 33% of myxoinflammatory fibroblastic sarcoma (MIFS) cases.<ref name=":0">{{Cite journal|last=Hirose|first=Takeshi|last2=Chang|first2=Hsin‐Yi|last3=Saoud|first3=Carla|last4=Lefkowitz|first4=Robert A.|last5=Athanasian|first5=Edward|last6=Antonescu|first6=Cristina R.|date=2025-01|title=A Clinicopathologic and Molecular Reappraisal of Myxoinflammatory Fibroblastic Sarcoma—A Controversial and Pathologically Challenging Low‐Grade Sarcoma|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.70018|journal=Genes, Chromosomes and Cancer|language=en|volume=64|issue=1|doi=10.1002/gcc.70018|issn=1045-2257}}</ref><ref name=":1">{{Cite journal|last=Kao|first=Yu-Chien|last2=Ranucci|first2=Valentina|last3=Zhang|first3=Lei|last4=Sung|first4=Yun-Shao|last5=Athanasian|first5=Edward A.|last6=Swanson|first6=David|last7=Dickson|first7=Brendan C.|last8=Antonescu|first8=Cristina R.|date=2017-11|title=Recurrent BRAF Gene Rearrangements in Myxoinflammatory Fibroblastic Sarcomas, but Not Hemosiderotic Fibrolipomatous Tumors|url=https://journals.lww.com/00000478-201711000-00002|journal=American Journal of Surgical Pathology|language=en|volume=41|issue=11|pages=1456–1465|doi=10.1097/PAS.0000000000000899|issn=0147-5185}}</ref><ref name=":2">{{Cite journal|last=Klubíčková|first=Natálie|last2=Agaimy|first2=Abbas|last3=Hájková|first3=Veronika|last4=Ptáková|first4=Nikola|last5=Grossmann|first5=Petr|last6=Šteiner|first6=Petr|last7=Michal|first7=Michal|last8=Michal|first8=Michael|date=2022-10|title=RNA-sequencing of myxoinflammatory fibroblastic sarcomas reveals a novel SND1::BRAF fusion and 3 different molecular aberrations with the potential to upregulate the TEAD1 gene including SEC23IP::VGLL3 and TEAD1::MRTFB gene fusions|url=https://link.springer.com/10.1007/s00428-022-03368-7|journal=Virchows Archiv|language=en|volume=481|issue=4|pages=613–620|doi=10.1007/s00428-022-03368-7|issn=0945-6317}}</ref><ref name=":3">{{Cite journal|last=Suster|first=David|last2=Michal|first2=Michael|last3=Huang|first3=Huiya|last4=Ronen|first4=Shira|last5=Springborn|first5=Stephanie|last6=Debiec-Rychter|first6=Maria|last7=Billings|first7=Steven D.|last8=Goldblum|first8=John R.|last9=Rubin|first9=Brian P.|date=2020-12|title=Myxoinflammatory fibroblastic sarcoma: an immunohistochemical and molecular genetic study of 73 cases|url=https://linkinghub.elsevier.com/retrieve/pii/S0893395222004227|journal=Modern Pathology|language=en|volume=33|issue=12|pages=2520–2533|doi=10.1038/s41379-020-0580-6}}</ref><ref name=":4">{{Cite journal|last=Harnisch|first=Kim|last2=Bode|first2=Beata|last3=Chijioke|first3=Obinna|last4=Hench|first4=Ivana Bratic|last5=Kazakov|first5=Dmitry V.|date=2025-12|title=Myxoinflammatory Fibroblastic Sarcoma, Nodular-Necrotizing Variant With Two YAP1::MAML2 Fusions and TRIM24::BRAF Fusion|url=https://journals.lww.com/10.1097/DAD.0000000000003107|journal=The American Journal of Dermatopathology|language=en|volume=47|issue=12|pages=976–978|doi=10.1097/DAD.0000000000003107|issn=0193-1091}}</ref><ref name=":5">{{Cite journal|last=Arbajian|first=Elsa|last2=Hofvander|first2=Jakob|last3=Magnusson|first3=Linda|last4=Mertens|first4=Fredrik|date=2020-05|title=Deep sequencing of myxoinflammatory fibroblastic sarcoma|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.22832|journal=Genes, Chromosomes and Cancer|language=en|volume=59|issue=5|pages=309–317|doi=10.1002/gcc.22832|issn=1045-2257}}</ref> Multiple fusion partners have been described, including ''TOM1L2, SND1, ZNF335, TRIM24'', and ''ROBO1''. In addition, ''TGFBR3-OGA (MGEA5)'' rearrangements, resulting from the t(1;10)(p22;q24) translocation, are detected in approximately 32% of cases.<ref name=":0" /><ref name=":5" /><ref name=":6">{{Cite journal|last=Lambert|first=Isabelle|last2=Debiec-Rychter|first2=Maria|last3=Guelinckx|first3=Paul|last4=Hagemeijer|first4=Anne|last5=Sciot|first5=Raf|date=2001-05|title=Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes|url=http://link.springer.com/10.1007/s004280000376|journal=Virchows Archiv|language=en|volume=438|issue=5|pages=509–512|doi=10.1007/s004280000376|issn=0945-6317}}</ref><ref name=":7">{{Cite journal|last=Hallor|first=Karolin H|last2=Sciot|first2=Raf|last3=Staaf|first3=Johan|last4=Heidenblad|first4=Markus|last5=Rydholm|first5=Anders|last6=Bauer|first6=Henrik CF|last7=Åström|first7=Kristina|last8=Domanski|first8=Henryk A|last9=Meis|first9=Jeanne M|date=2009-04|title=Two genetic pathways, t(1;10) and amplification of 3p11–12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions|url=https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.2513|journal=The Journal of Pathology|language=en|volume=217|issue=5|pages=716–727|doi=10.1002/path.2513|issn=0022-3417}}</ref><ref name=":8">{{Cite journal|last=Liu|first=Huifei|last2=Sukov|first2=William R.|last3=Ro|first3=Jae Y.|date=2019-02-01|title=The t(1;10)(p22;q24) TGFBR3/MGEA5 Translocation in Pleomorphic Hyalinizing Angiectatic Tumor, Myxoinflammatory Fibroblastic Sarcoma, and Hemosiderotic Fibrolipomatous Tumor|url=https://aplm.kglmeridian.com/view/journals/arpa/143/2/article-p212.xml|journal=Archives of Pathology & Laboratory Medicine|language=en|volume=143|issue=2|pages=212–221|doi=10.5858/arpa.2017-0412-RA|issn=0003-9985}}</ref><ref name=":9">{{Cite journal|last=Antonescu|first=Cristina R.|last2=Zhang|first2=Lei|last3=Nielsen|first3=G.Petur|last4=Rosenberg|first4=Andrew E.|last5=Cin|first5=Paola Dal|last6=Fletcher|first6=Christopher D. M.|date=2011-10|title=Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor|url=https://onlinelibrary.wiley.com/doi/10.1002/gcc.20897|journal=Genes, Chromosomes and Cancer|language=en|volume=50|issue=10|pages=757–764|doi=10.1002/gcc.20897|issn=1045-2257}}</ref><ref name=":10">{{Cite journal|last=Boland|first=Jennifer M.|last2=Folpe|first2=Andrew L.|date=2017-09|title=Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?|url=https://journals.lww.com/00125480-201709000-00004|journal=Advances in Anatomic Pathology|language=en|volume=24|issue=5|pages=268–277|doi=10.1097/PAP.0000000000000151|issn=1072-4109}}</ref><ref name=":11">{{Cite journal|last=Elco|first=Christopher P.|last2=Mariño-Enríquez|first2=Adrián|last3=Abraham|first3=John A.|last4=Cin|first4=Paola Dal|last5=Hornick|first5=Jason L.|date=2010-11|title=Hybrid Myxoinflammatory Fibroblastic Sarcoma/Hemosiderotic Fibrolipomatous Tumor: Report of a Case Providing Further Evidence for a Pathogenetic Link|url=https://journals.lww.com/00000478-201011000-00021|journal=American Journal of Surgical Pathology|language=en|volume=34|issue=11|pages=1723–1727|doi=10.1097/PAS.0b013e3181f17d51|issn=0147-5185}}</ref><ref name=":12">{{Cite journal|last=Zreik|first=Riyam T.|last2=Carter|first2=Jodi M.|last3=Sukov|first3=William R.|last4=Ahrens|first4=William A.|last5=Fritchie|first5=Karen J.|last6=Montgomery|first6=Elizabeth A.|last7=Weiss|first7=Sharon W.|last8=Folpe|first8=Andrew L.|date=2016-07|title=TGFBR3 and MGEA5 rearrangements are much more common in “hybrid” hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817716000678|journal=Human Pathology|language=en|volume=53|pages=14–24|doi=10.1016/j.humpath.2016.02.005}}</ref><ref name=":13">{{Cite journal|last=Carter|first=Jodi M.|last2=Sukov|first2=William R.|last3=Montgomery|first3=Elizabeth|last4=Goldblum|first4=John R.|last5=Billings|first5=Steven D.|last6=Fritchie|first6=Karen J.|last7=Folpe|first7=Andrew L.|date=2014-09|title=TGFBR3 and MGEA5 Rearrangements in Pleomorphic Hyalinizing Angiectatic Tumors and the Spectrum of Related Neoplasms|url=https://journals.lww.com/00000478-201409000-00003|journal=American Journal of Surgical Pathology|language=en|volume=38|issue=9|pages=1182–1992|doi=10.1097/PAS.0000000000000212|issn=0147-5185}}</ref> ''YAP1::MAML2'' fusions are characteristic of the “nodular necrotizing” variant of MIFS and can co-exist with BRAF fusions.<ref name=":0" /><ref name=":14">{{Cite journal|last=Perret|first=Raul|last2=Tallegas|first2=Matthias|last3=Velasco|first3=Valérie|last4=Soubeyran|first4=Isabelle|last5=Coindre|first5=Jean-Michel|last6=Azmani|first6=Rihab|last7=Baud|first7=Jessica|last8=Bacle|first8=Guillaume|last9=De Pinieux|first9=Gonzague|date=2022-10|title=Recurrent YAP1::MAML2 fusions in “nodular necrotizing” variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases|url=https://linkinghub.elsevier.com/retrieve/pii/S089339522200254X|journal=Modern Pathology|language=en|volume=35|issue=10|pages=1398–1404|doi=10.1038/s41379-022-01096-6}}</ref> More recently, several novel fusions have been described, including ''RRAGB::CCNB3, FGFR1::ZBTB47, SEC23IP::VGLL3'', and ''TEAD1::MRTFB''.<ref name=":0" /><ref name=":2" />
{| 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)
|''BRAF'' <ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" />
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|''TOM1L2::BRAF'' <ref name=":1" />; ''SND1::BRAF''<ref name=":2" />; ''ZNF335::BRAF''<ref name=":3" />; ''TRIM24::BRAF''<ref name=":4" />; ''ROBO1::BRAF''<ref name=":5" />  
|<span class="blue-text">EXAMPLE:</span> D, P, T
|Fusion leads to constitutive activation of the MAPK (MEK/ERK) pathway
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|Variable; partner dependent
|<span class="blue-text">EXAMPLE:</span>
|Recurrent (33%) <ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" />
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, T<ref name=":2" />
|Yes (WHO) 
|Potential sensitivity to MEK inhibitors<ref name=":2" />  
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|''TGFBR3''<ref name=":0" /><ref name=":5" /><ref name=":6" /><ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /><ref name=":11" /><ref name=":12" /><ref name=":13" /> 
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|''TGFBR3-OGA (MGEA5)'' 
|<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''.
|Translocation t(1;10) does not result in a fusion transcript <ref name=":5" /><ref name=":7" /> but results in transcriptional dysregulation related to breakpoint rearrangement; altered TGF-β signaling modulation and transcriptionally activated of nearby genes to ''OGA'' including ''FGF8'', ''NPM3 ''as a consequence of the rearrangement 
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|Balanced or unbalanced t(1;10)(p22;q24); hybrid MIFS/ Haemosiderotic fibrohistiocytic lipomatous lesion (HFLT) with der(10)t(1;10)  
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|32% of pure MIFS<ref name=":0" /> 
|<span class="blue-text">EXAMPLE:</span> D
|D 
|
|Yes (WHO) 
|<span class="blue-text">EXAMPLE:</span>
|Recurrent in HFLT, PHAT, and subsets of MIFS; supports neoplastic nature<ref name=":9" /><ref name=":10" /><ref name=":11" /> Frequently identified in hybrid HFLT/MIFS lesions<ref name=":12" /><ref name=":13" />  
 
''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''
|''YAP1''<ref name=":0" /><ref name=":4" /><ref name=":14" />
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|''YAP1::MAML2''  
|Activates transcriptional programs related to proliferation and survival (Hippo pathway dysregulation)
|Variable


''YAP1'' locus in 11q22.1 and ''MAML2'' in 11q21<ref name=":14" />


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).
Involving exon 6 of ''YAP1'' and exon 2 of ''MAML2''<ref name=":4" />
|Recurrent in 7 cases  
|D
|No
|Characteristic of nodular necrotizing MIFS<ref name=":4" />
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|''RRAGB''<ref name=":0" />
|<span class="blue-text">EXAMPLE:</span> N/A
|''RRAGB::CCNB3''  
|<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.
|Likely dysregulation of cell cycle signaling
|<span class="blue-text">EXAMPLE:</span> N/A
|Intra-chromosomal X, includes exons 1–6 of ''RRAGB'' and the entire coding sequencing of ''CCNB3''
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|Rare, 1 case
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D  
|
|No
|
|Newly described
|-
|-
|
|''FGFR1''<ref name=":0" />
|
|''FGFR1::ZBTB47''
|
|Possible activation of FGFR signaling
|
|t(3;8)(p22.1; p11.23). The fusion transcript is composed of the ''FGFR1'' exons1–17 and ''ZBTB47'' exons 2–6
|
|Rare, 1 case
|
|D, T
|
|No
|
|Possible therapeutic relevance
|-
|''VGLL3''<ref name=":2" />
|''SEC23IP::VGLL3''
|Upregulation of TEAD-mediated transcription (Hippo pathway)
|Involving exon 2 of ''SEC23IP'' and exon 2 of ''VGLL3''
|Rare, 2 cases
|D
|No
|Alternative mechanism of ''VGLL3'' activation
|-
|''TEAD1''<ref name=":2" />
|''TEAD1::MRTFB''
|TEAD pathway activation
|Involving exon 9 of ''TEAD1'' and exon 13 of ''MRTFB''
|Rare, 1 case
|D
|No
|Supports Hippo pathway involvement
|}
|}
==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>
Chromosome 3 amplification involving ''VGLL3'' and ''CHMP2B'' is the most common genetic alteration in MIFS.<ref name=":0" /><ref name=":1" /><ref name=":5" /><ref name=":7" /><ref name=":9" />  
{| 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>
|3<ref name=":0" /><ref name=":1" /><ref name=":5" /><ref name=":7" /><ref name=":9" />
7
|Amplification
|<span class="blue-text">EXAMPLE:</span> Loss
|3p11–12
|<span class="blue-text">EXAMPLE:</span>
|''VGLL3, CHMP2B''
chr7
|D, P  
|<span class="blue-text">EXAMPLE:</span>
|Yes (WHO)
Unknown
|Present in majority of MIFS; associated with increased recurrence and metastasis risk<ref name=":0" />
|<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>
|9<ref name=":5" />
8
|Homozygous deletion
|<span class="blue-text">EXAMPLE:</span> Gain
|9p21
|<span class="blue-text">EXAMPLE:</span>
|''CDKN2A/B''
chr8
|<nowiki>- </nowiki>
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|<nowiki>- </nowiki>
|<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>
|13<ref name=":5" />
17
|Loss
|<span class="blue-text">EXAMPLE:</span> Amp
|13q14
|<span class="blue-text">EXAMPLE:</span>
|''RB1''  
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<nowiki>- </nowiki>
|<span class="blue-text">EXAMPLE:</span>
|No
''ERBB2''
|<nowiki>- </nowiki>
|<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.
|-
|
|
|
|
|
|
|
|}
|}
==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>
{| 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>
|Complex copy number alterations<ref name=":0" /><ref name=":5" /><ref name=":7" />
Co-deletion of 1p and 18q
|Multiple amplifications and deletions
|<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).
|Common  
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|D
|<span class="blue-text">EXAMPLE:</span> D, P
|No
|
|<nowiki>- </nowiki>
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
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|<span class="blue-text">EXAMPLE:</span>''EGFR''
|NA
 
|NA
<br />
|NA
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|NA
|<span class="blue-text">EXAMPLE:</span> Oncogene
|NA
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|NA
|<span class="blue-text">EXAMPLE:</span> T
|NA
|<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).
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|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
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|<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.
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|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
==Epigenomic Alterations==
Put your text here
No specific recurrent epigenetic modification pattern has been defined in MIFS.
 
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
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|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|''VGLL3'' amplification
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|Hippo–TEAD signaling  
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|TEAD-driven tumor initiation and progression
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|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|''BRAF''; fusions
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|MAPK (MEK/ERK)
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Increased proliferation via ERK activation  
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|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|''TGFBR3::OGA'' (''MGEA5'') with ''FGF8'' upregulation
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|FGF signaling
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|Growth factor–mediated proliferation  
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|''YAP1::MAML2''
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|Hippo pathway
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|Enhanced transcription of pro-proliferative genes  
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|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
 
* '''Fluorescence ''In Situ'' Hybridization (FISH)'''
** ''TGFBR3'' and ''OGA'' (''MGEA5'') rearrangement analysis using FISH using break-apart probes is the primary diagnostic tool for detecting the t(1;10)(p22;q24).  
** ''VGLL3'' amplification can also be detected by FISH on chromosome 3p12.1.  
 
* '''Karyotyping'''  
** Can identify:
*** t(1;10)(p22;q24)
*** Unbalanced der(10)t(1;10) chromosomes in hybrid MIFS/HFLT
*** Chromosome 3 with 3p11–12 amplification
 
* '''RNA Sequencing'''  
** ''BRAF'' gene fusions with associated partners ''TOM1L2, SND1, ZNF335, TRIM24'', and ''ROBO1''
** ''YAP1::MAML2''
** Other rare fusions ''RRAGB::CCNB3, FGFR1::ZBTB47, SEC23IP::VGLL3'', and ''TEAD1::MRTFB''  
** Identify fusion transcripts associated with the t(1;10) rearrangement. However: The t(1;10) translocation may not always generate functional fusion transcripts.  
 
* '''Real-Time Quantitative PCR (RT-qPCR)'''  
** Expression of ''VGLL3'' and ''CHMP2B'' associated with 3p amplification  
 
==Familial Forms==
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
No hereditary or germline predisposition syndrome has been associated with MIFS.  
 
==Additional Information==
==Additional Information==
Put your text here
NA
==Links==
==Links==
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
NA
==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
<references />
 
==Notes==
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  
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