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Egan, Caoimhe; Nicolae, Alina; Lack, Justin; Chung, Hye-Jung; Skarshaug, Shannon; Pham, Thu Anh; Navarro, Winnifred; Abdullaev, Zied; Aguilera, Nadine S; Xi, Liqiang; Pack, Svetlana; Pittaluga, Stefania; Jaffe, Elaine S; Raffeld, Mark
Haematologica (Roma), 04/2020, Letnik: 105, Številka: 4Journal Article
Histiocytic sarcoma is a rare malignant neoplasm that may occur or in the context of a previous hematologic malignancy or mediastinal germ cell tumor. Here, we performed whole exome sequencing and RNA-sequencing (RNA-Seq) on 21 archival cases of primary histiocytic sarcoma. We identified a high number of genetic alterations within the RAS/RAF/MAPK pathway in 21 of 21 cases, with alterations in (6 of 21), (5 of 21), (4 of 21), (4 of 21), (4 of 21), (1 of 21), and (1 of 21), including single cases with homozygous deletion of , high-level amplification of , and a novel fusion. Concurrent and mutations were present in 3 of 21 cases, and 5 of 7 cases with alterations in and/or had disease involving the gastrointestinal tract. Following unsupervised clustering of gene expression data, cases with and/or abnormalities formed a distinct tumor subgroup. A subset of wild-type cases had frequent mutations in B-cell lymphoma associated genes and/or clonal IG gene rearrangements. Our findings expand the current understanding of the molecular pathogenesis of this rare tumor and suggest the existence of a distinct subtype of primary histiocytic sarcoma characterized by alterations with predilection for the gastrointestinal tract.
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