PMID- 31135487
OWN - NLM
STAT- MEDLINE
DCOM- 20200406
LR  - 20201001
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 10
DP  - 2019 Oct
TI  - Cutaneous Syncytial Myoepithelioma Is Characterized by Recurrent EWSR1-PBX3 
      Fusions.
PG  - 1349-1354
LID - 10.1097/PAS.0000000000001286 [doi]
AB  - Cutaneous syncytial myoepithelioma (CSM) is a rare but distinctive benign variant 
      in the family of myoepithelial neoplasms of skin and soft tissue. CSM has unique 
      morphologic and immunohistochemical features, characterized by intradermal 
      syncytial growth of spindled, ovoid, and histiocytoid cells and consistent 
      staining for S-100 protein and EMA, and differs from other myoepithelial tumors 
      by showing only infrequent keratin staining. Rearrangement of the EWSR1 gene is 
      now known to occur in up to half of all skin and soft tissue myoepithelial 
      tumors, with a wide family of documented fusion partners. In 2013, we reported 
      frequent (80%) EWSR1 rearrangements in CSM, but were unable to identify the 
      fusion partner using available studies at that time. After recent identification 
      of an index case of CSM harboring an EWSR1-PBX3 fusion, we used a combination of 
      targeted RNA sequencing and fluorescence in situ hybridization (FISH) studies to 
      investigate the genetic features of a cohort of CSM. An EWSR1-PBX3 fusion was 
      identified in all 13 cases successfully tested. RNA sequencing was successful in 
      8/13 cases, all of which were found to have identical breakpoints fusing exon 8 
      of EWSR1 to exon 5 of PBX3. FISH confirmed both EWSR1 and PBX3 rearrangements in 
      9/9 cases tested, which included 4 confirmed to have EWSR1-PBX3 fusion by 
      RNA-Seq, 3 cases that failed RNA-Seq, and 2 cases examined by FISH alone. Two 
      cases failed RNA sequencing but had no additional tissue remaining for FISH 
      studies. Our findings demonstrate that EWSR1-PBX3 fusions occur in most (and 
      possibly all) cases of CSM.
FAU - Jo, Vickie Y
AU  - Jo VY
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA.
FAU - Antonescu, Cristina R
AU  - Antonescu CR
AD  - Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Dickson, Brendan C
AU  - Dickson BC
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
FAU - Swanson, David
AU  - Swanson D
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Fletcher, Christopher D M
AU  - Fletcher CDM
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA.
FAU - Demicco, Elizabeth G
AU  - Demicco EG
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
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  - 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 (EWSR1 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 146150-81-4 (proto-oncogene protein Pbx3)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*genetics
MH  - Female
MH  - *Gene Fusion
MH  - *Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Myoepithelioma/*genetics/pathology
MH  - Proto-Oncogene Proteins/*genetics
MH  - RNA-Binding Protein EWS/*genetics
MH  - Sequence Analysis, RNA
MH  - Skin Neoplasms/*genetics/pathology
MH  - Young Adult
PMC - PMC6742566
MID - NIHMS1527517
COIS- Financial disclosure and conflict of interest: The authors declare no relevant 
      conflicts of interest. This project was supported in part by: P50 CA140146-01 
      (CRA); P50 CA217694 (CRA); P30-CA008748 (CRA); Kristen Ann Carr Foundation (CRA); 
      Cycle for Survival (CRA).
EDAT- 2019/05/29 06:00
MHDA- 2020/04/09 06:00
PMCR- 2020/10/01
CRDT- 2019/05/29 06:00
PHST- 2019/05/29 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/05/29 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000001286 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Oct;43(10):1349-1354. doi: 10.1097/PAS.0000000000001286.