PMID- 26691015
OWN - NLM
STAT- MEDLINE
DCOM- 20160810
LR  - 20180712
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 238
IP  - 4
DP  - 2016 Mar
TI  - FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma.
PG  - 502-7
LID - 10.1002/path.4683 [doi]
AB  - Calcifying aponeurotic fibroma (CAF) is a soft tissue neoplasm with a 
      predilection for the hands and feet in children and adolescents. Its molecular 
      basis is unknown. We used chromosome banding analysis, fluorescence in situ 
      hybridization (FISH), mRNA sequencing (RNA-seq), RT-PCR, and immunohistochemistry 
      to characterize a series of CAFs. An insertion ins(2;4)(q35;q25q?) was identified 
      in the index case. Fusion of the FN1 and EGF genes, mapping to the breakpoint 
      regions on chromosomes 2 and 4, respectively, was detected by RNA-seq and 
      confirmed by RT-PCR in the index case and two additional cases. FISH on five 
      additional tumours identified FN1-EGF fusions in all cases. CAFs analysed by 
      RT-PCR showed that FN1 exon 23, 27 or 42 was fused to EGF exon 17 or 19. 
      High-level expression of the entire FN1 gene in CAF suggests that strong FN1 
      promoter activity drives inappropriate expression of the biologically active 
      portion of EGF, which was detected immunohistochemically in 8/9 cases. The 
      FN1-EGF fusion, which has not been observed in any other neoplasm, appears to be 
      the main driver mutation in CAF. Although further functional studies are required 
      to understand the exact pathogenesis of CAF, the composition of the chimera 
      suggests an autocrine/paracrine mechanism of transformation. Copyright (c) 2015 
      Pathological Society of Great Britain and Ireland. Published by John Wiley & 
      Sons, Ltd.
CI  - Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Puls, Florian
AU  - Puls F
AD  - Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS 
      Foundation Trust, Birmingham, UK.
FAU - Hofvander, Jakob
AU  - Hofvander J
AD  - Department of Clinical Genetics, University and Regional Laboratories, Skane 
      University Hospital, Lund University, Lund, Sweden.
FAU - Magnusson, Linda
AU  - Magnusson L
AD  - Department of Clinical Genetics, University and Regional Laboratories, Skane 
      University Hospital, Lund University, Lund, Sweden.
FAU - Nilsson, Jenny
AU  - Nilsson J
AD  - Department of Clinical Genetics, University and Regional Laboratories, Skane 
      University Hospital, Lund University, Lund, Sweden.
FAU - Haywood, Elaine
AU  - Haywood E
AD  - Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS 
      Foundation Trust, Birmingham, UK.
FAU - Sumathi, Vaiyapuri P
AU  - Sumathi VP
AD  - Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS 
      Foundation Trust, Birmingham, UK.
FAU - Mangham, D Chas
AU  - Mangham DC
AD  - Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS 
      Foundation Trust, Birmingham, UK.
AD  - Department of Histopathology, Robert Jones & Agnes Hunt Orthopaedic Hospital, 
      Oswestry, UK.
FAU - Kindblom, Lars-Gunnar
AU  - Kindblom LG
AD  - Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS 
      Foundation Trust, Birmingham, UK.
FAU - Mertens, Fredrik
AU  - Mertens F
AD  - Department of Clinical Genetics, University and Regional Laboratories, Skane 
      University Hospital, Lund University, Lund, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (FN1 protein, human)
RN  - 0 (Fibronectins)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Banding/methods
MH  - Epidermal Growth Factor/*genetics
MH  - Exons
MH  - Female
MH  - Fibroma/genetics/*pathology
MH  - Fibronectins/*genetics
MH  - Gene Fusion
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Male
MH  - Recurrence
MH  - Soft Tissue Neoplasms/*genetics/*pathology
OTO - NOTNLM
OT  - calcifying aponeurotic fibroma
OT  - epidermal growth factor
OT  - fibronectin
OT  - gene fusion
OT  - juvenile aponeurotic fibroma
OT  - soft tissue neoplasm
EDAT- 2015/12/23 06:00
MHDA- 2016/08/11 06:00
CRDT- 2015/12/23 06:00
PHST- 2015/11/16 00:00 [received]
PHST- 2015/12/03 00:00 [revised]
PHST- 2015/12/14 00:00 [accepted]
PHST- 2015/12/23 06:00 [entrez]
PHST- 2015/12/23 06:00 [pubmed]
PHST- 2016/08/11 06:00 [medline]
AID - 10.1002/path.4683 [doi]
PST - ppublish
SO  - J Pathol. 2016 Mar;238(4):502-7. doi: 10.1002/path.4683.