Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing
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Date
2015
Journal Title
Journal ISSN
Volume Title
Publisher
Laboratory investigation
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 (RNASeq)
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.
Description
Keywords
Gene fusion detection, Paraffin-embedded benign fibrous histiocytomas, Fluorescence, Situ hybridization, RNA sequencing
Citation
Walther, C., Hofvander, J., Nilsson, J., Magnusson, L., Domanski, H. A., Gisselsson, D., ... & Mertens, F. (2015). Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing. Laboratory investigation, 95(9), 1071-1076. doi:10.1038/labinvest.2015.83