@article{Caoimhe Egan_Alina Nicolae_Justin Lack_Hye-Jung Chung_Shannon Skarshaug_Thu Anh Pham_Winnifred Navarro_Zied Abdullaev_Nadine S. Aguilera_Liqiang Xi_Svetlana Pack_Stefania Pittaluga_Elaine S. Jaffe_Mark Raffeld_2020, place={Pavia, Italy}, title={Genomic profiling of primary histiocytic sarcoma reveals two molecular subgroups}, volume={105}, url={https://haematologica.org/article/view/9331}, DOI={10.3324/haematol.2019.230375}, abstractNote={Histiocytic sarcoma is a rare malignant neoplasm that may occur <em>de novo</em> 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 <em>NF1</em> (6 of 21), <em>MAP2K1</em> (5 of 21), <em>PTPN11</em> (4 of 21), <em>BRAF</em> (4 of 21), <em>KRAS</em> (4 of 21), <em>NRAS</em> (1 of 21), and <em>LZTR1</em> (1 of 21), including single cases with homozygous deletion of <em>NF1</em>, high-level amplification of <em>PTPN11</em>, and a novel <em>TTYH3-BRAF</em> fusion. Concurrent <em>NF1</em> and <em>PTPN11</em> mutations were present in 3 of 21 cases, and 5 of 7 cases with alterations in <em>NF1</em> and/or <em>PTPN11</em> had disease involving the gastrointestinal tract. Following unsupervised clustering of gene expression data, cases with <em>NF1</em> and/or <em>PTPN11</em> abnormalities formed a distinct tumor subgroup. A subset of <em>NF1/PTPN11</em> 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 <em>NF1/PTPN11</em&gt; alterations with predilection for the gastrointestinal tract.}, number={4}, journal={Haematologica}, author={Caoimhe Egan and Alina Nicolae and Justin Lack and Hye-Jung Chung and Shannon Skarshaug and Thu Anh Pham and Winnifred Navarro and Zied Abdullaev and Nadine S. Aguilera and Liqiang Xi and Svetlana Pack and Stefania Pittaluga and Elaine S. Jaffe and Mark Raffeld}, year={2020}, month={Mar.}, pages={951-960} }