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Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma.

Płaszczyca, Anna ; Nilsson, Jenny LU ; Magnusson, Linda LU ; Brosjö, Otte ; Larsson, Olle ; Vult von Steyern, Fredrik LU ; Domanski, Henryk LU ; Lilljebjörn, Henrik LU orcid ; Fioretos, Thoas LU and Tayebwa, Johnbosco LU , et al. (2014) In International Journal of Biochemistry & Cell Biology 53(Apr 8). p.475-481
Abstract
Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are... (More)
Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through their many phosphorylation targets are implicated in a variety of cellular processes, as well as tumor development. When inactive, the amino-terminal, regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon activation, which requires several steps, they typically translocate to cell membranes, where they interact with different signaling pathways. The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic mechanism should result in constitutive kinase activity at an ectopic location. The results show that BFH indeed is a true neoplasm, and that distorted PKC activity is essential for tumorigenesis. The findings also provide means to differentiate BFH from other skin and soft tissue tumors. This article is part of a Directed Issue entitled: Rare cancers. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Biochemistry & Cell Biology
volume
53
issue
Apr 8
pages
475 - 481
publisher
Elsevier
external identifiers
  • pmid:24721208
  • wos:000340340400057
  • scopus:84904969139
ISSN
1878-5875
DOI
10.1016/j.biocel.2014.03.027
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Clinical Genetics (013022003), Pathology, (Lund) (013030000), Department of Orthopaedics (Lund) (013028000)
id
e400db59-c675-4d8d-ada6-6c2add7bcb07 (old id 4430389)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24721208?dopt=Abstract
date added to LUP
2016-04-01 10:26:55
date last changed
2022-04-20 02:11:43
@article{e400db59-c675-4d8d-ada6-6c2add7bcb07,
  abstract     = {{Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through their many phosphorylation targets are implicated in a variety of cellular processes, as well as tumor development. When inactive, the amino-terminal, regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon activation, which requires several steps, they typically translocate to cell membranes, where they interact with different signaling pathways. The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic mechanism should result in constitutive kinase activity at an ectopic location. The results show that BFH indeed is a true neoplasm, and that distorted PKC activity is essential for tumorigenesis. The findings also provide means to differentiate BFH from other skin and soft tissue tumors. This article is part of a Directed Issue entitled: Rare cancers.}},
  author       = {{Płaszczyca, Anna and Nilsson, Jenny and Magnusson, Linda and Brosjö, Otte and Larsson, Olle and Vult von Steyern, Fredrik and Domanski, Henryk and Lilljebjörn, Henrik and Fioretos, Thoas and Tayebwa, Johnbosco and Mandahl, Nils and Hansén Nord, Karolin and Mertens, Fredrik}},
  issn         = {{1878-5875}},
  language     = {{eng}},
  number       = {{Apr 8}},
  pages        = {{475--481}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Biochemistry & Cell Biology}},
  title        = {{Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma.}},
  url          = {{http://dx.doi.org/10.1016/j.biocel.2014.03.027}},
  doi          = {{10.1016/j.biocel.2014.03.027}},
  volume       = {{53}},
  year         = {{2014}},
}