Genomic alterations

The tumor usually has a characteristic cytogenetic translocation t(12;15)(p13;q25) to create the ETV6::NTRK3 fusion gene. Infantile fibrosarcoma shares this translocation and a virtually identical histological appearance with mesoblastic nephroma.

Infantile fibrosarcoma occasionally occurs in children up to age 4 years. A tumor with similar morphology has been identified in older children. In these older children, the tumors do not have the ETV6::NTRK3 fusion that is characteristic of the tumors in younger patients.[84] BRAF intragenic deletions have been described in cases of infantile fibrosarcoma. Some of these tumors also contained NTRK3 fusions.[85] One study described four young children (aged 2–10 years) with tumors that were histologically classified as infantile fibrosarcoma and had ALK rearrangements.[86]

The Associazione Italiana Ematologia Oncologia Pediatrica analyzed a cohort of 44 pediatric patients with tumors classified as infantile fibrosarcomas/congenital mesoblastic nephromas. Eight infantile fibrosarcoma–like mesenchymal tumors found to be negative for the ETV6::NTRK3 fusion gene were analyzed by RNA sequencing to identify novel driver events. They identified three fusion genes involving RAF1: GOLGA4::RAF1, LRRFIP2::RAF1, and CLIP1::RAF1. The three fusion proteins retained the entire catalytic domain of the RAF1 kinase.[87]