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Somatic mutations in histiocytic sarcoma identified by next generation sequencing

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Abstract

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20–72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 “Hotspot” oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

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Author notes

  1. Qingqing Liu

    Present address: Department of Pathology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, USA

  2. Hongbo Yu

    Present address: Pathology and Laboratory Medicine Service, VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA, 02132, USA

Authors and Affiliations

  1. Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA

    Qingqing Liu, Keith Tomaszewicz, Lloyd Hutchinson, Bruce Woda & Hongbo Yu

  2. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Jason L. Hornick

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  1. Qingqing Liu
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Correspondence to Hongbo Yu.

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This study was approved by the Institutional Review Board of University of Massachusetts Medical School.

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The authors declare that they have no conflict of interest.

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Liu, Q., Tomaszewicz, K., Hutchinson, L. et al. Somatic mutations in histiocytic sarcoma identified by next generation sequencing. Virchows Arch 469, 233–241 (2016). https://doi.org/10.1007/s00428-016-1965-2

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  • DOI: https://doi.org/10.1007/s00428-016-1965-2

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