title: A transcriptome signature of endothelial lymphatic cells coexists with the chronic oxidative stress signature in radiation-induced post-radiotherapy breast angiosarcomas.
abstract: Radiation-induced breast angiosarcomas are rare but recognized complication of breast cancer radiotherapy and are of poor prognosis. Little is known about the genetic abnormalities present in these secondary tumors. Herein, we investigated the differences in the genome and in the transcriptome that discriminate these tumors as a function of their etiology. Seven primary breast angiosarcomas and 18 secondary breast angiosarcomas arising in the irradiation field of a radiotherapy were analyzed. Copy number alterations and gene expression were analyzed using Affymetrix SNP 6.0 Array and Affymetrix Exon Arrays, respectively. We showed that two transcriptome signatures of the radiation tumorigenesis coexisted in these tumors. One was histology specific and correctly discriminated 100% of the primary tumors from the radiation-induced tumors. The deregulation of marker genes, including podoplanin (PDPN), prospero homeobox 1 (PROX-1), vascular endothelial growth factor 3 (VEGFR3) and endothelin receptor A (EDNRA), suggests that the radiation-induced breast angiosarcomas developed from radiation-stimulated lymphatic endothelial cells. None of the genes of the histology-specific signature were present in our previously published signature of the radiation tumorigenesis which shows the presence of a chronic oxidative stress in radiation-induced sarcomas of various histologies. Nevertheless, this oxidative stress signature classified correctly 88% of the breast angiosarcomas as a function of the etiology. In contrast, MYC amplification, which is observed in all radiation-induced tumors but also at a low rate in primary tumors, was not a marker of the radiation tumorigenesis.
authors.affiliation: Institut Curie, Centre de Recherche, UMR3244, 26 Rue d'Ulm Paris Cedex 5 F-75248, France.
authors.forename: Nabila-Sandra
authors.initials: NS
authors.lastname: Hadj-Hamou
authors.forename: Marick
authors.initials: M
authors.lastname: Laé
authors.forename: Anna
authors.initials: A
authors.lastname: Almeida
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.forename: Youlia
authors.initials: Y
authors.lastname: Kirova
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Bernard
authors.initials: B
authors.lastname: Malfoy
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000532:radiotherapy; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006394:Hemangiosarcoma / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome