Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions. (November 2018)

• Record Type: Journal Article
• Authors: Dadone-Montaudié, Bérengère; Alberti, Laurent; Duc, Adeline; Delespaul, Lucile; Lesluyes, Tom; Pérot, Gaëlle; Lançon, Agnès; Paindavoine, Sandrine; Di Mauro, Ilaria; Blay, Jean-Yves; Fouchardière, Arnaud; Chibon, Frédéric; Karanian, Marie; MacGrogan, Gaëtan; Kubiniek, Valérie; Keslair, Frédérique; Cardot-Leccia, Nathalie; Michot, Audrey; Perrin, Virginie; Zekri, Yanis; Coindre, Jean-Michel; Tirode, Franck; Pedeutour, Florence; Ranchère-Vince, Dominique; Le Loarer, François; Pissaloux, Daniel
• Is Part Of: Modern pathology. Volume 31:Number 11(2018)
• Page Start: 1683
• Page End: 1693
• Publication Date: 2018-11
• Subjects: Pathology -- Periodicals; Diagnosis, Laboratory -- Periodicals; Pathologie -- Périodiques; Diagnostics biologiques -- Périodiques; Diagnosis, Laboratory; Pathology; Pathology -- Abstracts; Pathology -- Periodicals; Periodicals; Electronic journals; 616.07
• DOI: 10.1038/s41379-018-0089-4
• Languages: English
• ISSNs: 0893-3952

Abstract

Abstract Dermatofibrosarcoma protuberans is underlined by recurrentcollagen type I alpha 1 chain- platelet-derived growth factor B chain (COL1A1-PDGFB ) fusions but ~ 4% of typical dermatofibrosarcoma protuberans remain negative for this translocation in routine molecular screening. We investigated a series of 21 cases not associated with the pathognomonicCOL1A1-PDGFB fusion on routine fluorescence in situ hybridization (FISH) testing. All cases displayed morphological and clinical features consistent with the diagnosis of dermatofibrosarcoma protuberans. RNA-sequencing analysis was successful in 20 cases. The classicalCOL1A1-PDGFB fusion was present in 40% of cases (n = 8/20), and subsequently confirmed with aCOL1A1 break-apart FISH probe in all but one case (n = 7/8). 55% of cases (n = 11/20) displayed novelPDGFD rearrangements;PDGFD being fused either to the 5′ part ofCOL6A3 (2q37.3) (n = 9/11) orEMILIN2 (18p11) (n = 2/11). All rearrangements led to in-frame fusion transcripts and were confirmed at genomic level by FISH and/or array-comparative genomic hybridization.PDGFD -rearranged dermatofibrosarcoma protuberans presented clinical outcomes similar to typical dermatofibrosarcoma protuberans. Notably, the twoEMILIN2-PDGFD cases displayed fibrosarcomatous transformation and homozygous deletions ofCDKN2A at genomic level. We report the first recurrent molecular variant of dermatofibrosarcoma protuberans involvingPDGFD, which functionally mimic bona fide COL1A1-PDGFB fusions, leading presumably to a similar autocrine loop-stimulating PDGFRB. This study also emphasizes thatCOL1A1-PDGFB fusions can be cytogenetically cryptic on FISH testing in a subset of cases, thereby representing a diagnostic pitfall that pathologists should be aware of.