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FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma.

Puls, Florian; Hofvander, Jakob LU ; Magnusson, Linda LU ; Nilsson, Jenny LU ; Haywood, Elaine; Sumathi, Vaiyapuri P; Mangham, D Chas; Kindblom, Lars-Gunnar and Mertens, Fredrik LU (2016) In Journal of Pathology 238(4). p.502-507
Abstract
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, were detected by RNA-seq and confirmed by RT-PCR in the index case and two additional cases. FISH on five additional tumour identified FN1-EGF fusions in all cases. CAFs analysed by RT-PCR showed that FN1 exon 23, 27 or 42 were fused to... (More)
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, were detected by RNA-seq and confirmed by RT-PCR in the index case and two additional cases. FISH on five additional tumour identified FN1-EGF fusions in all cases. CAFs analysed by RT-PCR showed that FN1 exon 23, 27 or 42 were 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Pathology
volume
238
issue
4
pages
502 - 507
publisher
John Wiley & Sons
external identifiers
  • pmid:26691015
  • scopus:84959216048
  • wos:000370840000004
ISSN
0022-3417
DOI
10.1002/path.4683
language
English
LU publication?
yes
id
95f22923-2e73-4ff0-b2bf-8ceee9d78e52 (old id 8504071)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26691015?dopt=Abstract
date added to LUP
2016-01-06 11:43:35
date last changed
2017-04-16 04:19:25
@article{95f22923-2e73-4ff0-b2bf-8ceee9d78e52,
  abstract     = {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, were detected by RNA-seq and confirmed by RT-PCR in the index case and two additional cases. FISH on five additional tumour identified FN1-EGF fusions in all cases. CAFs analysed by RT-PCR showed that FN1 exon 23, 27 or 42 were 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.},
  author       = {Puls, Florian and Hofvander, Jakob and Magnusson, Linda and Nilsson, Jenny and Haywood, Elaine and Sumathi, Vaiyapuri P and Mangham, D Chas and Kindblom, Lars-Gunnar and Mertens, Fredrik},
  issn         = {0022-3417},
  language     = {eng},
  number       = {4},
  pages        = {502--507},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pathology},
  title        = {FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma.},
  url          = {http://dx.doi.org/10.1002/path.4683},
  volume       = {238},
  year         = {2016},
}