PMID- 30720533
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20200501
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 5
DP  - 2019 May
TI  - Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 
      Distinct Gene Fusions and Phenotype.
PG  - 695-702
LID - 10.1097/PAS.0000000000001227 [doi]
AB  - Primary intraosseous rhabdomyosarcomas (RMSs) are extremely rare. Recently 2 
      studies reported 4 cases of primary intraosseous RMS with EWSR1/FUS-TFCP2 gene 
      fusions, associated with somewhat conflicting histologic features, ranging from 
      spindle to epithelioid. In this study we sought to further investigate the 
      pathologic and molecular abnormalities of a larger group of intraosseous RMSs by 
      a combined approach using targeted RNA sequencing analysis and fluorescence in 
      situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in 
      young adults, age range 20 to 39 years (median, 27 y). Three cases involved the 
      pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. 
      Molecular studies identified recurrent gene fusions in all 7 cases tested, 
      including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases, and 
      FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, 
      without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2-positive cases were 
      characterized by a more primitive and fascicular spindle cell appearance, while 
      the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, 
      with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. 
      Immunohistochemically, all tumors were positive for desmin and myogenin (focal). 
      In addition, 4 tumors with TFCP2-associated gene fusions also coexpressed ALK and 
      cytokeratin. In conclusion, our results suggest a high incidence of gene fusions 
      in primary RMSs of bone, with 2 molecular subsets emerging, defined by either 
      MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and 
      immunophenotype. Additional studies with larger numbers of cases and longer 
      follow-up data are required to definitively evaluate the biological behavior of 
      these tumors and to establish their relationship to other spindle cell RMS 
      genetic groups.
FAU - Agaram, Narasimhan P
AU  - Agaram NP
AD  - Departments of Pathology.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Departments of Pathology.
FAU - Sung, Yun-Shao
AU  - Sung YS
AD  - Departments of Pathology.
FAU - Cavalcanti, Marcela S
AU  - Cavalcanti MS
AD  - Neopath Dx Diagnostic Pathology Laboratory, Curitiba, Parana, Brazil.
FAU - Torrence, Dianne
AU  - Torrence D
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida, Gainesville, FL.
FAU - Wexler, Leonard
AU  - Wexler L
AD  - Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Francis, Glenn
AU  - Francis G
AD  - Genomics for Life.
FAU - Sommerville, Scott
AU  - Sommerville S
AD  - The Wesley Hospital.
FAU - Swanson, David
AU  - Swanson D
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
FAU - Dickson, Brendan C
AU  - Dickson BC
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
FAU - Suurmeijer, Albert J H
AU  - Suurmeijer AJH
AD  - Department of Pathology, University Medical Center, University of Groningen, 
      Groningen, The Netherlands.
FAU - Williamson, Richard
AU  - Williamson R
AD  - Medlab Pathology, Brisbane, Qld, Australia.
FAU - Antonescu, Cristina R
AU  - Antonescu CR
AD  - Departments of Pathology.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA140146/CA/NCI NIH HHS/United States
GR  - P50 CA217694/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EWSR1 protein, human)
RN  - 0 (FUS protein, human)
RN  - 0 (MEIS1 protein, human)
RN  - 0 (Myeloid Ecotropic Viral Integration Site 1 Protein)
RN  - 0 (NCOA2 protein, human)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 0 (TFCP2 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adult
MH  - Biomarkers, Tumor/*genetics
MH  - Bone Neoplasms/*genetics/pathology
MH  - DNA-Binding Proteins/genetics
MH  - Female
MH  - *Gene Fusion
MH  - *Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Myeloid Ecotropic Viral Integration Site 1 Protein/genetics
MH  - Nuclear Receptor Coactivator 2/genetics
MH  - Phenotype
MH  - RNA-Binding Protein EWS/genetics
MH  - RNA-Binding Protein FUS/genetics
MH  - Rhabdomyosarcoma/*genetics/pathology
MH  - Sequence Analysis, RNA
MH  - Transcription Factors/genetics
MH  - Young Adult
PMC - PMC6613942
MID - NIHMS1533010
EDAT- 2019/02/06 06:00
MHDA- 2020/02/20 06:00
PMCR- 2020/05/01
CRDT- 2019/02/06 06:00
PHST- 2019/02/06 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2019/02/06 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000001227 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 May;43(5):695-702. doi: 10.1097/PAS.0000000000001227.