STBT5:CIC-rearranged sarcoma

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Primary Author(s)*

Ganesh P. Pujari, M.D, FICC and Katherine Geiersbach, M.D.

WHO Classification of Disease

(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)

Structure Disease
Book
Category
Family
Type
Subtype(s)

Definition / Description of Disease

Previously grouped into Ewing and other primitive sarcoma categories, it was not until 2006 that the CIC-rearranged sarcomas were identified as a distinct subgroup of soft tissue neoplasms in the “Ewing-like sarcomas” category. Apart from the classical DUX4, approximately 8 other partner genes have been reported so far. [1] Overall due to its characteristic histomorphologic and immunophenotypic features, diagnostic molecular rearrangements, highly aggressive clinical course, poor response to chemotherapy and adverse outcome (compared to Ewing sarcoma) CIC-rearranged sarcoma has been recognized as a distinct pathologic entity by the WHO under the category of undifferentiated small round cell sarcomas of bone and soft tissue and grouped along with the sarcoma with BCOR genetic alterations, and round cell sarcoma with EWSR1::non-ETS fusions. [2]

Synonyms / Terminology

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Epidemiology / Prevalence

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Clinical Features

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Signs and Symptoms EXAMPLE: Asymptomatic (incidental finding on complete blood counts)

EXAMPLE: B-symptoms (weight loss, fever, night sweats)

EXAMPLE: Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE: Cytopenias

EXAMPLE: Lymphocytosis (low level)

Sites of Involvement

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Morphologic Features

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Immunophenotype

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Finding Marker
Positive (universal) EXAMPLE: CD1
Positive (subset)
Negative (universal)
Negative (subset)

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

EXAMPLE: Yes EXAMPLE: No EXAMPLE: Yes EXAMPLE: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).

Individual Region Genomic Gain / Loss / LOH

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Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:7 EXAMPLE: Loss EXAMPLE:chr7:1-159,335,973 [hg38] EXAMPLE:chr7 EXAMPLE: Yes EXAMPLE: Yes EXAMPLE: No EXAMPLE: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 reference).
EXAMPLE:8 EXAMPLE: Gain EXAMPLE:chr8:1-145,138,636 [hg38] EXAMPLE:chr8 EXAMPLE: No EXAMPLE: No EXAMPLE: No EXAMPLE:Common recurrent secondary finding for t(8;21) (add reference).

Characteristic Chromosomal Patterns

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Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:Co-deletion of 1p and 18q EXAMPLE: Yes EXAMPLE: No EXAMPLE: No EXAMPLE:See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE: Yes EXAMPLE: No EXAMPLE: No EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

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Genes and Main Pathways Involved

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Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program

Genetic Diagnostic Testing Methods

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Familial Forms

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Additional Information

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Links

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References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

  1. Makise, Naohiro; et al. (2024-03). "CIC-Rearranged Sarcoma". Surgical Pathology Clinics. 17 (1): 141–151. doi:10.1016/j.path.2023.06.003. ISSN 1875-9157. PMID 38278603 Check |pmid= value (help). Check date values in: |date= (help)
  2. WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours. Lyon (France): International Agency for Research on Cancer; 2020. (WHO classification of tumours series, 5th ed.; vol. 3). https://publications.iarc.fr/588.