Infantile Fibrosarcoma (IFS)
Overview
Infantile fibrosarcoma is a pediatric soft-tissue sarcoma occurring predominantly in the first two years of life, classified under Soft Tissue Sarcoma in OncoTree (parent: SOFT_TISSUE). It is defined by the ETV6–NTRK3 fusion in ~90% of cases and has a favorable prognosis compared to adult fibrosarcoma, being responsive to TRK inhibitors.
Cohorts in the corpus
- sarcoma_ucla_2024: SARC0127 was initially suspected as IFS but PDTO larotrectinib resistance and FISH-negative ETV6 results led to reclassification as SCSRMS (spindle cell/sclerosing rhabdomyosarcoma) — demonstrating that functional PDTO screening delivered a diagnostic signal within one week vs 18 days for pathology. The 24-subtype UCLA sarcoma biobank included IFS among 194 specimens from 126 patients (Feb 2018–May 2022). PMID:39305899
Recurrent alterations
- ETV6–NTRK3 fusion: canonical driver, present in ~90% of IFS. FISH-negative ETV6 status in SARC0127 helped redirect diagnosis from IFS to SCSRMS. PMID:39305899
- NTRK1, NTRK2, NTRK3: relevant TRK family members assessed by FISH in the UCLA study. PMID:39305899
- PIPseq cohort: EML4-NTRK3 fusion detected in a congenital fibrosarcoma patient, supporting diagnostic reclassification from undifferentiated sarcoma to infantile fibrosarcoma; fusion is an ALK-inhibitor target PMID:28007021
Subtypes
- ETV6–NTRK3-positive (~90%)
- ETV6–NTRK3-negative / rare alternate fusions
Therapeutic landscape
- larotrectinib: TRK inhibitor that is the standard targeted therapy for ETV6–NTRK3-positive IFS. SARC0127 PDTOs were resistant to larotrectinib, which correctly predicted the absence of the ETV6–NTRK3 fusion and prompted reclassification as SCSRMS. PMID:39305899
Sources
- PMID:39305899 — Al Shihabi et al. Cell Stem Cell 2024. UCLA sarcoma PDTO drug-sensitivity landscape.
This page was processed by crosslinker on 2026-05-04. - PMID:28007021
This page was processed by wiki-cli on 2026-05-14.