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Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing.

Walther, Charles LU ; Hofvander, Jakob LU ; Nilsson, Jenny LU ; Magnusson, Linda LU ; Domanski, Henryk LU ; Gisselsson Nord, David LU ; Tayebwa, Johnbosco LU ; Doyle, Leona A; Fletcher, Christopher Dm and Mertens, Fredrik LU (2015) In Laboratory Investigation 95(9). p.1071-1076
Abstract
Benign fibrous histiocytomas (FH) can be subdivided into several morphological and clinical subgroups. Recently, gene fusions involving either one of two protein kinase C genes (PRKCB and PRKCD) or the ALK gene were described in FH. We here wanted to evaluate the frequency of PRKCB and PRKCD gene fusions in FH. Using interphase fluorescence in situ hybridization on sections from formalin-fixed paraffin-embedded (FFPE) tumors, 36 cases could be analyzed. PRKCB or PRKCD rearrangements were seen in five tumors: 1/7 regular, 0/3 aneurysmal, 0/6 cellular, 2/7 epithelioid, 0/1 atypical, 2/10 deep, and 0/2 metastatic lesions. We also evaluated the status of the ALK gene in selected cases, finding rearrangements in 3/7 epithelioid and 0/1 atypical... (More)
Benign fibrous histiocytomas (FH) can be subdivided into several morphological and clinical subgroups. Recently, gene fusions involving either one of two protein kinase C genes (PRKCB and PRKCD) or the ALK gene were described in FH. We here wanted to evaluate the frequency of PRKCB and PRKCD gene fusions in FH. Using interphase fluorescence in situ hybridization on sections from formalin-fixed paraffin-embedded (FFPE) tumors, 36 cases could be analyzed. PRKCB or PRKCD rearrangements were seen in five tumors: 1/7 regular, 0/3 aneurysmal, 0/6 cellular, 2/7 epithelioid, 0/1 atypical, 2/10 deep, and 0/2 metastatic lesions. We also evaluated the status of the ALK gene in selected cases, finding rearrangements in 3/7 epithelioid and 0/1 atypical lesions. To assess the gene fusion status of FH further, deep sequencing of RNA (RNA-Seq) was performed on FFPE tissue from eight cases with unknown gene fusion status, as well as on two FH and six soft tissue sarcomas with known gene fusions; of the latter eight positive controls, the expected fusion transcript was found in all but one, while 2/8 FH with unknown genetic status showed fusion transcripts, including a novel KIRREL/PRKCA chimera. Thus, also a third member of the PRKC family is involved in FH tumorigenesis. We conclude that gene fusions involving PRKC genes occur in several morphological (regular, cellular, aneurysmal, epithelioid) and clinical (cutaneous, deep) subsets of FH, but they seem to account for only a minority of the cases. In epithelioid lesions, however, rearrangements of PRKC or ALK were seen, as mutually exclusive events, in the majority (5/7) of cases. Finally, the study also shows that RNA-Seq is a promising tool for identifying gene fusions in FFPE tissues.Laboratory Investigation advance online publication, 29 June 2015; doi:10.1038/labinvest.2015.83. (Less)
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published
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in
Laboratory Investigation
volume
95
issue
9
pages
1071 - 1076
publisher
Nature Publishing Group
external identifiers
  • pmid:26121314
  • wos:000360402900009
  • scopus:84940373344
ISSN
1530-0307
DOI
10.1038/labinvest.2015.83
language
English
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yes
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2b2667dc-c44f-42fd-b45a-55d922b7df01 (old id 7477365)
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http://www.ncbi.nlm.nih.gov/pubmed/26121314?dopt=Abstract
date added to LUP
2015-07-11 10:48:57
date last changed
2017-10-22 03:22:37
@article{2b2667dc-c44f-42fd-b45a-55d922b7df01,
  abstract     = {Benign fibrous histiocytomas (FH) can be subdivided into several morphological and clinical subgroups. Recently, gene fusions involving either one of two protein kinase C genes (PRKCB and PRKCD) or the ALK gene were described in FH. We here wanted to evaluate the frequency of PRKCB and PRKCD gene fusions in FH. Using interphase fluorescence in situ hybridization on sections from formalin-fixed paraffin-embedded (FFPE) tumors, 36 cases could be analyzed. PRKCB or PRKCD rearrangements were seen in five tumors: 1/7 regular, 0/3 aneurysmal, 0/6 cellular, 2/7 epithelioid, 0/1 atypical, 2/10 deep, and 0/2 metastatic lesions. We also evaluated the status of the ALK gene in selected cases, finding rearrangements in 3/7 epithelioid and 0/1 atypical lesions. To assess the gene fusion status of FH further, deep sequencing of RNA (RNA-Seq) was performed on FFPE tissue from eight cases with unknown gene fusion status, as well as on two FH and six soft tissue sarcomas with known gene fusions; of the latter eight positive controls, the expected fusion transcript was found in all but one, while 2/8 FH with unknown genetic status showed fusion transcripts, including a novel KIRREL/PRKCA chimera. Thus, also a third member of the PRKC family is involved in FH tumorigenesis. We conclude that gene fusions involving PRKC genes occur in several morphological (regular, cellular, aneurysmal, epithelioid) and clinical (cutaneous, deep) subsets of FH, but they seem to account for only a minority of the cases. In epithelioid lesions, however, rearrangements of PRKC or ALK were seen, as mutually exclusive events, in the majority (5/7) of cases. Finally, the study also shows that RNA-Seq is a promising tool for identifying gene fusions in FFPE tissues.Laboratory Investigation advance online publication, 29 June 2015; doi:10.1038/labinvest.2015.83.},
  author       = {Walther, Charles and Hofvander, Jakob and Nilsson, Jenny and Magnusson, Linda and Domanski, Henryk and Gisselsson Nord, David and Tayebwa, Johnbosco and Doyle, Leona A and Fletcher, Christopher Dm and Mertens, Fredrik},
  issn         = {1530-0307},
  language     = {eng},
  number       = {9},
  pages        = {1071--1076},
  publisher    = {Nature Publishing Group},
  series       = {Laboratory Investigation},
  title        = {Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing.},
  url          = {http://dx.doi.org/10.1038/labinvest.2015.83},
  volume       = {95},
  year         = {2015},
}