PMID- 29955147 OWN - NLM STAT- MEDLINE DCOM- 20190821 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 31 IP - 11 DP - 2018 Nov TI - Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions. PG - 1683-1693 LID - 10.1038/s41379-018-0089-4 [doi] AB - 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. FAU - Dadone-Montaudie, Berengere AU - Dadone-Montaudie B AD - Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, Universite Cote d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Alberti, Laurent AU - Alberti L AD - Cancer Research Center of Lyon, Universite Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Lyon, France. AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Duc, Adeline AU - Duc A AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Delespaul, Lucile AU - Delespaul L AD - INSERM U1218 ACTION, Bordeaux, France. AD - University of Bordeaux, Bordeaux, France. AD - INSERM U1037, Cancer Research Center of Toulouse (CRCT), Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. FAU - Lesluyes, Tom AU - Lesluyes T AD - INSERM U1218 ACTION, Bordeaux, France. AD - University of Bordeaux, Bordeaux, France. AD - INSERM U1037, Cancer Research Center of Toulouse (CRCT), Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. FAU - Perot, Gaelle AU - Perot G AD - Department of Pathology, Institut Bergonie, Bordeaux, France. FAU - Lancon, Agnes AU - Lancon A AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Paindavoine, Sandrine AU - Paindavoine S AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Di Mauro, Ilaria AU - Di Mauro I AD - Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, Universite Cote d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Blay, Jean-Yves AU - Blay JY AD - Cancer Research Center of Lyon, Universite Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Lyon, France. AD - Department of Oncology, Centre Leon Berard, Lyon, France. FAU - de la Fouchardiere, Arnaud AU - de la Fouchardiere A AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Chibon, Frederic AU - Chibon F AUID- ORCID: 0000-0002-6548-2181 AD - INSERM U1218 ACTION, Bordeaux, France. AD - Department of Pathology, Institut Bergonie, Bordeaux, France. AD - INSERM U1037, Cancer Research Center of Toulouse (CRCT), Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. FAU - Karanian, Marie AU - Karanian M AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - MacGrogan, Gaetan AU - MacGrogan G AD - Department of Pathology, Institut Bergonie, Bordeaux, France. FAU - Kubiniek, Valerie AU - Kubiniek V AD - Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, Universite Cote d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Keslair, Frederique AU - Keslair F AD - Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, Universite Cote d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Cardot-Leccia, Nathalie AU - Cardot-Leccia N AD - Central Laboratory of Pathology, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Michot, Audrey AU - Michot A AD - Department of Surgery, Institut Bergonie, Bordeaux, France. FAU - Perrin, Virginie AU - Perrin V AD - Department of Translational Research and Innovation, Centre Leon Berard, Lyon, France. FAU - Zekri, Yanis AU - Zekri Y AD - Department of Translational Research and Innovation, Centre Leon Berard, Lyon, France. FAU - Coindre, Jean-Michel AU - Coindre JM AD - University of Bordeaux, Bordeaux, France. AD - Department of Pathology, Institut Bergonie, Bordeaux, France. FAU - Tirode, Franck AU - Tirode F AUID- ORCID: 0000-0003-4731-7817 AD - Cancer Research Center of Lyon, Universite Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Lyon, France. AD - Department of Translational Research and Innovation, Centre Leon Berard, Lyon, France. FAU - Pedeutour, Florence AU - Pedeutour F AD - Laboratory of Solid Tumors Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, Universite Cote d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. FAU - Ranchere-Vince, Dominique AU - Ranchere-Vince D AD - Department of Biopathology, Centre Leon Berard, Lyon, France. FAU - Le Loarer, Francois AU - Le Loarer F AD - University of Bordeaux, Bordeaux, France. AD - Department of Pathology, Institut Bergonie, Bordeaux, France. FAU - Pissaloux, Daniel AU - Pissaloux D AD - Cancer Research Center of Lyon, Universite Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Lyon, France. daniel.pissaloux@lyon.unicancer.fr. AD - Department of Biopathology, Centre Leon Berard, Lyon, France. daniel.pissaloux@lyon.unicancer.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180628 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (COL1A1 protein, human) RN - 0 (COLIA1-PDGFB fusion protein, human) RN - 0 (Collagen Type I, alpha 1 Chain) RN - 0 (Lymphokines) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (PDGFD protein, human) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Proto-Oncogene Proteins c-sis) MH - Adult MH - Aged MH - Child, Preschool MH - Collagen Type I, alpha 1 Chain MH - Dermatofibrosarcoma/*genetics MH - Female MH - Gene Rearrangement MH - Humans MH - Lymphokines/*genetics MH - Male MH - Middle Aged MH - Oncogene Proteins, Fusion/genetics MH - Platelet-Derived Growth Factor/*genetics MH - Proto-Oncogene Proteins c-sis/genetics MH - Skin Neoplasms/*genetics EDAT- 2018/06/30 06:00 MHDA- 2019/08/23 06:00 CRDT- 2018/06/30 06:00 PHST- 2018/02/13 00:00 [received] PHST- 2018/05/07 00:00 [accepted] PHST- 2018/05/07 00:00 [revised] PHST- 2018/06/30 06:00 [pubmed] PHST- 2019/08/23 06:00 [medline] PHST- 2018/06/30 06:00 [entrez] AID - S0893-3952(22)60007-3 [pii] AID - 10.1038/s41379-018-0089-4 [doi] PST - ppublish SO - Mod Pathol. 2018 Nov;31(11):1683-1693. doi: 10.1038/s41379-018-0089-4. Epub 2018 Jun 28.