A systematic review of the prevalence of pathogenic or likely pathogenic germline variants in individuals with FOXO1 fusion‐positive rhabdomyosarcoma

Abstract

Several cancer predisposition syndromes (CPS) are reported to predispose to rhabdomyosarcoma, most frequently in children with embryonal rhabdomyosarcoma. There are lingering questions over the role of CPS in individuals with alveolar rhabdomyosarcoma (ARMS), which are frequently driven by FOXO1 fusion oncoproteins. We conducted a systematic review to identify patients with FOXO1 fusion‐positive ARMS (FP‐ARMS) who underwent germline DNA sequencing. We estimated the prevalence of pathogenic/likely pathogenic (P/LP) variants in cancer predisposing genes (CPGs) and of CPSs. We included 19 publications reporting on 191 patients with FP‐ARMS. P/LP variants in CPGs were identified in 26/191 (13.6%) patients, nine (4.9%) of which were associated with a CPS diagnosis. Evidence for causal associations between CPSs and FP‐ARMS could not be assessed with available data from this review. Only one patient was affected with a CPS known to predispose to rhabdomyosarcoma, Li–Fraumeni syndrome. Typical CPS associations with rhabdomyosarcoma are rare, but not nonexistent, in patients with FP‐ARMS. FOXO1 fusion status, alone, is insufficient for clinicians to rely on to distinguish between patients with/without CPS.

MLIP and its Influence on Key Oncogenic Pathways: Implications for Cancer Therapeutics

“…This helps to prevent the development of cancer by eliminating cells with damaged DNA 42 . However, in cancer cells, the activity of FOXO1 and FOXO3 is often dysregulated [43][44][45] . In tumors, FOXO expression or activity is often suppressed to promote cell proliferation and survival, or alternatively FOXO may be activated to promote cell migration and invasion [43][44][45] .…”

MLIP and Its Potential Influence on Key Oncogenic Pathways

“…This helps to prevent the development of cancer by eliminating cells with damaged DNA [91]. However, in cancer cells, the activity of FOXO1 and FOXO3 is often dysregulated [92][93][94]. In tumors, FOXO expression or activity is often suppressed to promote cell proliferation and survival, or alternatively, FOXO may be activated to promote cell migration and invasion [92][93][94].…”