Novel COL4A1‐VEGFD gene fusion in myofibroma

Abstract

Myofibroma are benign soft-tissue tumours mostly found in young children. These neoplasms belong to the pericytic/perivascular tumour family in the WHO classification, based on shared histologic characteristics. 1 The clinical presentation features solitary or multiple tumours involving the skin, muscles, bones and internal organs.The multicentric form of the disease, referred to as infantile myofibromatosis (IMF), can be a life-threatening condition when visceral nodules are present. 2 Unlike children, adult patients develop only solitary myofibroma. 3 The diagnosis of myofibroma, based on pathological examination, can be challenging. Recently, we and others discovered oncogenic mutations in PDGFRB, encoding platelet-derived growth factor receptor beta, a receptor tyrosine kinase which is essential for pericyte development. 3,4 In a 69-case series, we showed that oncogenic variants of PDGFRB were present in 68% of IMF and 24% of isolated myofibromas. PDGFRB mutations have also been found in myopericytoma, a closely related entity, but not in other soft-tissue tumours. 5 These findings opened the possibility of treating severe myofibromatosis with tyrosine kinase inhibitors that target PDGFRB. Two such drugs, imatinib and sunitinib,

SRF Rearrangements in Soft Tissue Tumors with Muscle Differentiation

“…Other genetic alterations involving SRF gene fused to CITED1 , CITED2 , NFKBIE or NCOA2 ( Figure 6 b–d) were observed in perivascular myoid tumors [ 5 ] and myofibromas [ 9 ]. Moreover, SRF::NCOA2 fusion-positive pediatric RMS (rhabdomyosarcoma) showing diffuse staining for desmin and multifocal nuclear positivity for myogenin are reported ( Figure 6 d) [ 23 , 24 ].…”

“…Translocation events involving the SRF gene have been described in literature for different types of soft tissue tumors. Indeed, SRF is often fused to various 3′ partner genes, including RELA [ 4 , 5 , 6 ], ICA1L [ 7 ], FOXO [ 8 ] and STAT6 [ 9 ], leading to the production of aberrant transcription factors and thus to the enrichment of SRF -involving pathways.…”

Identification of a novel PHIP::BRAF gene fusion in infantile fibrosarcoma

“…The verification of the raw RNA‐seq read quality was performed on FastQC (version 0.11.9). Reads were then aligned to the GRCh37 reference genome via STAR aligner (version 2.7.2d) in a two‐mode process as described 8 . Fusion genes were called using STAR‐Fusion (version 1.9.0) and FusionCatcher (version 1.10) 9,10 .…”

“…Reads were then aligned to the GRCh37 reference genome via STAR aligner (version 2.7.2d) in a two-mode process as described. 8 Fusion genes were called using STAR-Fusion (version 1.9.0) and FusionCatcher (version 1.10). 9,10 The selected gene fusion was detected by both softwares and had at least one JunctionReadCount and one SpanningFragCount.…”

Solitary cutaneous infantile myofibroma as a hallmark of myofibromatosis: Two cases and review of the literature

“…3 NOTCH3 variants and SRF fusions, among other mutations, have been reported as well while some tumors do not have identifiable mutations. 1,4 IM is categorized as solitary, multicentric, or generalized. Solitary IM is the most common, representing 50-80% of patients.…”