Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Modern Pathology Année : 2018

Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions

Gaëtan Mac Grogan
  • Fonction : Auteur
  • PersonId : 918885
Yanis Zekri

Résumé

Dermatofibrosarcoma protuberans is underlined by recurrent collagen 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 pathognomonic COL1A1-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 classical COL1A1-PDGFB fusion was present in 40% of cases (n = 8/20), and subsequently confirmed with a COL1A1 break-apart FISH probe in all but one case (n = 7/8). 55% of cases (n = 11/20) displayed novel PDGFD rearrangements; PDGFD being fused either to the 5' part of COL6A3 (2q37.3) (n = 9/11) or EMILIN2 (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 two EMILIN2-PDGFD cases displayed fibrosarcomatous transformation and homozygous deletions of CDKN2A at genomic level. We report the first recurrent molecular variant of dermatofibrosarcoma protuberans involving PDGFD, which functionally mimic bona fide COL1A1-PDGFB fusions, leading presumably to a similar autocrine loop-stimulating PDGFRB. This study also emphasizes that COL1A1-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.
Fichier principal
Vignette du fichier
2108.ModPathol.DFSP.Dadone.pdf (8.4 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

inserm-02440547 , version 1 (15-01-2020)

Identifiants

Citer

Bérengère Dadone-Montaudié, Laurent Alberti, Adeline Duc, Lucile Delespaul, Tom Lesluyes, et al.. Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions. Modern Pathology, 2018, 31 (11), pp.1683-1693. ⟨10.1038/s41379-018-0089-4⟩. ⟨inserm-02440547⟩
99 Consultations
202 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More