Compendium of Cancer Genome Aberrations

STBT5:Ewing sarcoma: Difference between revisions

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==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
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>
Ewing sarcoma is defined by fusions between a FET family gene (usually EWSR1 or rarely FUS/TAF15) and a member of the ETS family of transcription factors. These chimeric oncoproteins act as aberrant transcription factors and are required for tumorigenesis. Rare variant fusions involving non ETS partners have also been described.
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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)
|EWSR1||''EWSR1::FLI1''||FET–ETS chimeric transcription factor; binds GGAA microsatellites and canonical ETS sites, recruits chromatin regulators, opens closed chromatin to establish de novo enhancers and represses wild-type ETS targets, driving an oncogenic gene-expression program.||Classically t(11;22)(q24;q12); usually balanced but can be unbalanced or cryptic (e.g. insertional events).
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|Common (~85% of Ewing sarcomas)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|D
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
|The t(11;22)(q24;q12) rearrangement resulting in EWSR1::FLI1 is diagnostic of Ewing sarcoma in the appropriate clinical and morphological context (PMID: 1522903). This is the most common fusion, occurring in ~85% of cases. Although several transcript variants exist (e.g., Type 1 and Type 2), fusion subtype does not alter current management and is not used for risk stratification in modern protocols. Rare cryptic insertional variants may be FISH-negative, requiring RNA-based sequencing for detection
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).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|EWSR1
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|''EWSR1::ERG''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|t(21;22)(q22;q12) or complex/unbalanced rearrangements involving 21q22 and 22q12.
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|Recurrent (~10% of Ewing sarcomas)
|<span class="blue-text">EXAMPLE:</span> D
|D (±P)
|
|Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
|<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).
EWSR1::ERG accounts for ~10% of Ewing sarcomas and is most commonly produced through complex or unbalanced rearrangements. These structural variants can result in false-negative EWSR1 break-apart FISH, making ERG-specific FISH or RNA-based NGS essential when morphology and immunophenotype suggest Ewing sarcoma. Clinical behavior appears broadly similar to EWSR1::FLI1 fusions, although chromoplexy-associated cases show increased TP53 mutations in some series
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|''EWSR1''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|''EWSR1::ETV1''




Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
Other fusion partners include ''ETV4, FEV, E1AF, ZSG''
|<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> 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
|Various balanced or complex translocations/insertions involving ETS loci (7p21 for ETV1, 17q21 for ETV4, 2q36 for FEV).
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
t(7;22)(p22;q12)
|<span class="blue-text">EXAMPLE:</span> T
t(2;22)(q33;q12)
|
t(17;22)(q12;q12)
|<span class="blue-text">EXAMPLE:</span>
inv(22)(q12q12)
 
|Rare (<5% of Ewing sarcomas)
Both balanced and unbalanced forms are observed by FISH (add references).
|D (±P)
|Yes (WHO, NCCN)
|These rare FET–ETS fusions are diagnostic of Ewing sarcoma when identified in the correct clinical setting. All functionally mimic EWSR1::FLI1 by generating a chimeric ETS transcription factor that drives an oncogenic enhancer program. FEV-rearranged tumors may present in older patients, show a higher frequency of extraskeletal disease, and may be associated with more aggressive clinical behavior in limited published cohorts. ETV1/ETV4 fusions have been reported in very young children (<2 years).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|''FUS''
|<span class="blue-text">EXAMPLE:</span> N/A
|FUS::ERG
|<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.
Other fusion partners include FEV
|<span class="blue-text">EXAMPLE:</span> N/A
|FUS substitutes for EWSR1 within the FET family, forming FET–ETS fusion proteins with the same GGAA-microsatellite–driven chromatin reprogramming mechanism.
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|t(16;21)(p11;q22)
|<span class="blue-text">EXAMPLE:</span> D, P, T
Translocations involving 16p11 (FUS) and ETS loci (21q22 ERG, 2q36 FEV); balanced or complex.
|
|Rare (<5% of Ewing sarcomas)
|
|D (±P)
|Yes (WHO, NCCN)
|FUS-based fusions represent rare (<5%) molecular subsets of Ewing sarcoma in which FUS substitutes for EWSR1 within the FET family. Their presence confirms the diagnosis in cases lacking EWSR1 rearrangements. As with EWSR1-ERG, FUS-ERG cases may involve complex rearrangements that require RNA-based NGS for detection. FUS::FEV–positive tumors may show predilection for extraskeletal sites and worse outcomes compared to classic ES fusions in small studies.
|-
|-
|
|TAF15
|
|TAF15::ETS
|
|FET-family member forming FET–ETS chimeric transcription factors with analogous chromatin and transcriptional effects.
|
|Various translocations involving 17q12 (TAF15) and ETS loci.
|
|Rare (<5% of Ewing sarcomas)
|
|D
|
|Yes (WHO)
|
|TAF15–ETS fusions occur rarely and are considered genetic equivalents to EWSR1- and FUS-based FET–ETS rearrangements. Their identification supports a diagnosis of Ewing sarcoma when morphology and phenotype are appropriate. Because many TAF15 rearrangements are cryptic, RNA sequencing is often required. No distinct prognostic or therapeutic implications apart from those of conventional Ewing sarcoma are currently recognized.
|}
|}
==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>
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>
These copy-number alterations represent secondary genomic events that accompany the primary FET–ETS fusion. They are thought to reflect genome instability, replication stress buffering, or clonal selection, rather than defining molecular subtypes.
According to the WHO classification, the prognostic role of copy-number alterations remains under prospective validation.
https://pubmed.ncbi.nlm.nih.gov/41301081/<span style="color:#0070C0">)</span>
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|1
7
|Gain
|<span class="blue-text">EXAMPLE:</span> Loss
|1q21-q44 (arm-level); chr1q [hg38; ~90 Mb]
|<span class="blue-text">EXAMPLE:</span>
|Multiple (e.g., ''RAD21'', ''MDM4'')
chr7
|P
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Recurrent arm-level gain, frequently occurring with concurrent 16q loss; reflects increased copy-number burden and genomic instability.
|<span class="blue-text">EXAMPLE:</span> D, P
|-
|<span class="blue-text">EXAMPLE:</span> No
|16
|<span class="blue-text">EXAMPLE:</span>
|Loss
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).
| -16q11-q24 (arm-level); chr16q [hg38; ~45 Mb]
|Multiple
|P
|No
|Often paired with 1q gain as part of an unbalanced t(1;16); associated with inferior outcome in some cohorts.
|-
|8
|Gain
|Whole chromosome 8; chr8 [hg38; ~146 Mb]
|''RAD21, MYC (8q24)''
|P (uncertain)
|No
|One of the most frequent numerical aberrations; increased ''RAD21'' dosage may mitigate replication stress driven by EWSR1::FLI1; prognostic impact is variable.
|-
|12
|Gain
|Whole chromosome 12; chr12 [hg38; ~134 Mb]
|None recurrently amplified
|P (uncertain)
|No
|Recurrent trisomy reflecting mitotic mis-segregation; focal ''MDM2'' or ''CDK4'' amplification is not typical of Ewing sarcoma.
|-
|20
|Gain
|Whole chromosome 20; chr20 [hg38; ~64 Mb]
|Multiple
|P (uncertain)
|No
|Less frequent whole-chromosome gain; clinical significance remains unclear.
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|9
8
|Loss
|<span class="blue-text">EXAMPLE:</span> Gain
|9p21.3; [hg38; ~1 Mb]
|<span class="blue-text">EXAMPLE:</span>
|''CDKN2A'', ''CDKN2B''
chr8
|P (uncertain)
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Focal homozygous deletions remove key cell-cycle regulators; prognostic relevance remains under prospective validation.
|<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>
|11
17
|LOH
|<span class="blue-text">EXAMPLE:</span> Amp
|11q24-q25 (region including ''FLI1'')
|<span class="blue-text">EXAMPLE:</span>
|''FLI1'' (partner locus)
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|P
|<span class="blue-text">EXAMPLE:</span>
|No
''ERBB2''
|May arise near the fusion partner locus through local structural complexity; reflects genomic instability rather than a distinct subtype.
|<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.
|-
|-
|
|22
|
|LOH
|
|22q12 (region including ''EWSR1'')
|
|EWSR1
|
|P
|
|No
|
|Copy-number changes adjacent to the fusion locus may accompany complex rearrangements or chromoplexy events.
|}
|}
==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>
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> Beyond the primary FET–ETS fusion, recurrent numerical and structural aberrations (listed above) reflect genome instability rather than distinct tumour subtypes. The presence of metastases at diagnosis remains the most powerful prognostic factor.
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Hyperdiploidy / numerical chromosomal gains
Co-deletion of 1p and 18q
|Mitotic mis-segregation leading to whole-chromosome gains
|<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)
|P
|<span class="blue-text">EXAMPLE:</span> D, P
|No
|
|Frequently observed secondary event; reflects chromosomal instability rather than a distinct biological subtype.
|
|-
|Gain of odd-numbered chromosomes (e.g., 1, 7, 8, 12)
|Whole-chromosome gains arising from aneuploidy
|Common
|P (uncertain)
|No
|Includes recurrent gains of chromosomes 1q, 8, and 12; prognostic impact varies across cohorts.
|-
|1q gain with 16q loss
|Unbalanced translocation, most commonly t(1;16), resulting in arm-level copy-number imbalance
|Common
|P
|No
|One of the most frequent structural patterns; associated with increased copy-number burden and adverse outcome in some studies.
|-
|Complex karyotype / multiple copy-number alterations
|Accumulation of secondary structural and numerical aberrations during tumor evolution
|Recurrent
|P
|No
|Reflects genomic instability accompanying disease progression rather than defining a molecular subgroup.
|-
|Chromoplexy / clustered rearrangements near fusion loci
|Coordinated DNA breakage and rejoining events involving multiple chromosomal regions
|Recurrent
|P
|No
|Often involves regions flanking ''EWSR1'' and ETS partner genes; considered an early or progression-related genomic phenomenon.
|-
|Microsatellite instability (MSI)
|Defective mismatch repair
|Rare
|None
|No
|MSI-high phenotype is not a characteristic feature of Ewing sarcoma.
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Chromothripsis
Microsatellite instability - hypermutated
|Single catastrophic chromosomal shattering event
|
|Rare
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|P (uncertain)
|<span class="blue-text">EXAMPLE:</span> P, T
|No
|
|Reported in isolated cases; clinical significance remains unclear.
|
|-
|-
|
|Homologous recombination deficiency
|
|Impaired DNA double-strand break repair
|
|Rare
|
|None
|
|No
|
|Not a defining feature of Ewing sarcoma.
|}
|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''STAG2''


<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|LOF mutations or deletions
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Recurrent
|<span class="blue-text">EXAMPLE:</span> T
|P
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<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).
|Loss may confer chromosomal instability; associated with increased relapse risk in some studies.
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|CDKN2A
<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|Homozygous deletion
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|Recurrent
|<span class="blue-text">EXAMPLE:</span> P
|P
|
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|Coincides with 9p21 focal deletion; prognostic impact inconsistent
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|TP53
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|Pathogenic missense mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|Recurrent
|<span class="blue-text">EXAMPLE:</span> T
|P
|
|
|
|Rare; may indicate aggressive disease, may co‑occur with STAG2 alterations
|-
|-
|
|
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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
Put your text here FET–ETS fusion proteins act as aberrant transcription factors that broadly dysregulate gene expression. They bind GGAA microsatellites and canonical ETS binding sites, promoting a transition from closed to open chromatin through the establishment of de novo enhancers while displacing wild-type ETS factors at native regulatory elements. Together, these effects create a dominant oncogenic gene expression program that underlies tumor initiation. Although secondary epigenetic regulators, including chromatin modifiers and demethylases, have been implicated in the literature, their roles are not detailed in the WHO classification.
 
==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>
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>
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EWSR1::FLI1 and other FET–ETS fusions
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|Transcriptional regulation via aberrant ETS binding
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Establishes de novo enhancers and represses native ETS targets, resulting in a dominant oncogenic gene-expression program that initiates tumor development.
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|STAG2 (LOF)
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|Cohesin complex, chromatin organization
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Disruption of cohesin function leads to chromosomal instability and altered enhancer–promoter interactions; associated with adverse clinical outcome in some cohorts.
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|CDKN2A (homozygous deletion or inactivating mutations)
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|Cell‑cycle regulation
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|Loss of p16INK4a/p14ARF promotes unchecked cell cycle progression; prognostic relevance remains under prospective evaluation.
|-
|-
|
|TP53 (pathogenic missense mutations)
|
|DNA damage response and apoptosis
|
|Impaired cell cycle arrest and apoptotic signaling, may be associated with aggressive disease behavior.
|}
|}
==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>
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
Histopathology and IHC: Sheets of small round cells with strong membranous CD99 expression are characteristic; NKX2‑2, FLI1 and ERG expression may support diagnosis.
FISH: Ideally dual-color dual fusion for EWSR1 and common partner, but most institutions carry Dual‑color break‑apart probes for EWSR1 or FUS detect most rearrangements; however, complex inversions, insertions or rare partner fusions may escape detection.
RNA‑based assays (RT‑PCR or next‑generation sequencing): Necessary to identify specific fusion partners and to detect cryptic fusions negative by break‑apart FISH.
Copy‑number analysis: Low‑pass whole‑genome sequencing or cytogenomic microarrays can detect recurrent gains and losses (e.g., 1q gain/16q loss, trisomy 8, trisomy 12, CDKN2A deletion). Prognostic use of these CNAs is under investigation
==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>
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>
Ewing sarcoma is primarily sporadic.  Rare germline predisposition is noted in some cases, but no specific syndromes are detailed in the WHO guidelines. Investigations into germline variants (e.g., DNA repair genes) are ongoing.
==Additional Information==
==Additional Information==
Put your text here
Put your text here Prognosis: The presence of metastases at diagnosis and anatomical site (e.g., pelvic lesions) remain the strongest prognostic indicators. Copy‑number burden (e.g., 1q gain/16q loss) and mutations such as STAG2, CDKN2A and TP53 may contribute to risk stratification, but their significance is still being validated
 
pmc.ncbi.nlm.nih.gov
 
.
 
Treatment considerations: Current therapy consists of multi‑agent chemotherapy combined with surgery and/or radiation. No targeted agents are specifically approved for Ewing sarcoma in the WHO guideline; however, research is exploring personalized therapy, and clinical trials are exploring targeted and epigenetic therapies.
 
==Links==
==Links==
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
https://tumourclassification.iarc.who.int/welcome/
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1464
==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>
(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>
https://pubmed.ncbi.nlm.nih.gov/41301081/
==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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