STBT5:Infantile fibrosarcoma

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

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Primary Author(s)*

Kathleen Schieffer, PhD, FACMG

WHO Classification of Disease

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

Related Terminology

Acceptable	Congenital fibrosarcoma; infantile fibrosarcoma-like tumour; cellular congenital mesoblastic nephroma
Not Recommended	N/A

Gene Rearrangements

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Driver Gene	Fusion(s) and Common Partner Genes	Molecular Pathogenesis	Typical Chromosomal Alteration(s)	Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
NTRK3	ETV6	EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.	t(12;15)(p13;q25)	Common	D, T	Yes (WHO, NCCN)	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). BCR::ABL1 is generally favorable in CML (add reference).
NTRK3	EML4	EXAMPLE: 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.	None	Recurrent	D, T	Yes (WHO)	EXAMPLE: 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).
NTRK1	LMNA, TPM3, SQSTM1, MIR584F1	EXAMPLE: 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.	None	Recurrent	D, T	Yes (WHO)
NTRK3	SPECC1L	In-frame fusion that results in constitutive activation of the NTRK3 tyrosine kinase through heterodimerization and transphosphorylation of the SMC (structural maintenance of chromosomes) domain of SPECC1L. In this case, the breakpoint was in exon 9 of SPECC1L (NM_015330) and exon 13 of NTRK3 (NM_002530) and encompassed the entire tyrosine kinase domain of NTRK3.	None	Rare	D, T	No	A SPECC1L::NTRK3 fusion was reported in a single individual with a large infantile fibrosarcoma of the chest wall. The patient was treated with a TRK inhibitor (larotrectinib) with excellent clinical response.
BRAF	PT7, CUX1		None	Rare		No
BRAF	Deletion of CR1 domain and tandem duplication within exon 2	Intragenic gene rearrangement that is predicted to result in a constitutively active form of BRAF due to loss of the negative regulatory Ras-binding domain.	None	Rare		No
RET	CLIP2, MYH10		None	Rare		No
MET	TFG	In-frame fusion that is predicted to result in constitutive action of the MET tyrosine kinase domain through dimerization of the TFG dimerization domains. In this case, the breakpoint was in exon 7 of TFG and exon 15 of MET and encompassed the entire tyrosine kinase domain of MET.	None	Rare	D	Yes (WHO)	A TFG::MET fusion was reported in a single individual with an unusual infantile spindle cell sarcoma that morphologically resembled infantile fibrosarcoma. MET IHC showed diffuse expression with moderate intensity and RNA expression analysis indicated an intermediate overexpression of MET.

Individual Region Genomic Gain/Loss/LOH

Whole chromosome gain of 8, 11, 17, and 20 (in various combinations) are commonly observed in infantile fibrosarcoma.

Chr #	Gain, Loss, Amp, LOH	Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]	Relevant Gene(s)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
8	Gain	Whole chromosome 8	Unknown	D	No	Whole chromosome gain of 8 is commonly observed in infantile fibrosarcoma
11	Gain	Whole chromosome 11	Unknown	D	No	Whole chromosome gain of 11 is commonly observed in infantile fibrosarcoma
17	Gain	Whole chromosome 17	Unknown	D	No	Whole chromosome gain of 17 is commonly observed in infantile fibrosarcoma
20	Gain	Whole chromosome 20	Unknown	D	No	Whole chromosome gain of 20 is commonly observed in infantile fibrosarcoma

Characteristic Chromosomal or Other Global Mutational Patterns

None

Chromosomal Pattern	Molecular Pathogenesis	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes

Gene Mutations (SNV/INDEL)

None

Gene	Genetic Alteration	Tumor Suppressor Gene, Oncogene, Other	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes

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

Epigenomic Alterations

None

Genes and Main Pathways Involved

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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

• Fusion testing
  • Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels)
    • For targeted NGS panels, consider if the assay requires both gene partners to be included on the panel or if it is able to identify novel fusions as long as one of the partners is included on the panel
  • Whole transcriptome RNA-sequencing
    • Provides an unbiased approach to fusion calling
• Fluorescence in situ hybridization (FISH)
  • Break apart probes for ETV6 and/or NTRK3 will identify a rearrangement (ETV6::NTRK3) present in the majority of infantile fibrosarcoma. Consider other fusion partners is ETV6 FISH is negative.
• Karyotyping
  • Can identify the t(12;15) rearrangement as well as other commonly reported aneusomies (i.e. whole chromosome gains of 8, 11, 17, 20)
• DNA sequencing
  • Can identify the commonly reported aneusomies if copy number variant calling is performed
  • Currently, there are no recurrently described somatic variants for infantile fibrosarcoma

Familial Forms

None

Additional Information

None

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 Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s): *Citation of this Page: “Infantile fibrosarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/4/2025, https://ccga.io/index.php/STBT5:Infantile fibrosarcoma.