PMID- 36555836
OWN - NLM
STAT- MEDLINE
DCOM- 20230105
LR  - 20230418
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 24
DP  - 2022 Dec 19
TI  - Implementation of Copy Number Variations-Based Diagnostics in Morphologically 
      Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue.
LID - 10.3390/ijms232416196 [doi]
LID - 16196
AB  - In the last decade, new tumor entities have been described, including 
      EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain 
      further insights into the behavior of these tumors, we analyzed a spectrum of 
      EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and 
      molecular features in relation to their prognosis. We report five patients with 
      EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two 
      complex cystic bone lesions lacking morphological characteristics of SBC, and two 
      sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all 
      cases copy number variation (CNV) profiling and fusion analyses were performed. 
      All patients were male, three cystic lesions occurred in children (aged 10, 14, 
      and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis 
      revealed two FUS::NFATC2 rearrangements in two cystic lesions and three 
      EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 
      FISH revealed tumor cells with break-apart signal without amplification in one 
      complex cystic lesion and EWSR1 amplification in both sarcomas was documented. 
      CNV analysis showed simple karyotypes in all cystic lesions, while more complex 
      karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and 
      expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged 
      neoplasms. The study highlights the importance of combining radiology and 
      morphologic features with molecular aberrations. The use of additional molecular 
      methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in 
      providing a correct diagnosis and avoiding overtreatment.
FAU - Brcic, Iva
AU  - Brcic I
AUID- ORCID: 0000-0001-9847-0171
AD  - Diagnostic and Research Institute of Pathology, Medical University of Graz, 
      Comprehensive Cancer Centre, 8010 Graz, Austria.
FAU - Scheipl, Susanne
AU  - Scheipl S
AD  - Department of Orthopedics and Trauma, Medical University of Graz, Comprehensive 
      Cancer Centre, 8010 Graz, Austria.
FAU - Bergovec, Marko
AU  - Bergovec M
AD  - Department of Orthopedics and Trauma, Medical University of Graz, Comprehensive 
      Cancer Centre, 8010 Graz, Austria.
FAU - Leithner, Andreas
AU  - Leithner A
AUID- ORCID: 0000-0002-2598-2325
AD  - Department of Orthopedics and Trauma, Medical University of Graz, Comprehensive 
      Cancer Centre, 8010 Graz, Austria.
FAU - Szkandera, Joanna
AU  - Szkandera J
AD  - Division of Clinical Oncology, Department of Medicine, Medical University of 
      Graz, Comprehensive Cancer Centre, 8010 Graz, Austria.
FAU - Sotlar, Karl
AU  - Sotlar K
AD  - Institute of Pathology, Paracelsus Medical University Salzburg, 5020 Salzburg, 
      Austria.
FAU - Suda, Arnold J
AU  - Suda AJ
AD  - Department of Orthopedics and Trauma Surgery, AUVA Trauma Center Salzburg, 5010 
      Salzburg, Austria.
FAU - Smolle, Maria Anna
AU  - Smolle MA
AUID- ORCID: 0000-0003-1021-0899
AD  - Department of Orthopedics and Trauma, Medical University of Graz, Comprehensive 
      Cancer Centre, 8010 Graz, Austria.
FAU - Kraus, Tanja
AU  - Kraus T
AD  - Department of Orthopedics and Trauma, Medical University of Graz, Comprehensive 
      Cancer Centre, 8010 Graz, Austria.
FAU - Rosenberg, Andrew Eric
AU  - Rosenberg AE
AD  - Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL 
      33136, USA.
FAU - Liegl-Atzwanger, Bernadette
AU  - Liegl-Atzwanger B
AUID- ORCID: 0000-0003-2229-5535
AD  - Diagnostic and Research Institute of Pathology, Medical University of Graz, 
      Comprehensive Cancer Centre, 8010 Graz, Austria.
FAU - Igrec, Jasminka
AU  - Igrec J
AUID- ORCID: 0000-0003-0247-8393
AD  - Division of General Radiology, Department of Radiology, Medical University of 
      Graz, Comprehensive Cancer Centre, 8010 Graz, Austria.
LA  - eng
PT  - Journal Article
DEP - 20221219
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (EWSR1 protein, human)
RN  - 0 (FUS protein, human)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (NFATC2 protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - *Bone Neoplasms/diagnosis/genetics/pathology
MH  - DNA Copy Number Variations
MH  - In Situ Hybridization, Fluorescence
MH  - NFATC Transcription Factors/genetics
MH  - Oncogene Proteins, Fusion/genetics
MH  - RNA-Binding Protein EWS/genetics
MH  - RNA-Binding Protein FUS/genetics
MH  - *Sarcoma/diagnosis/genetics
MH  - *Soft Tissue Neoplasms/diagnosis
MH  - Transcription Factors
MH  - Child
MH  - Adolescent
MH  - Adult
MH  - Aged
PMC - PMC9784784
OTO - NOTNLM
OT  - EWSR1
OT  - FUS
OT  - NFATC2
OT  - alterations
OT  - copy number variations
OT  - sarcoma
OT  - simple bone cyst
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/19
CRDT- 2022/12/23 01:36
PHST- 2022/10/18 00:00 [received]
PHST- 2022/11/28 00:00 [revised]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2022/12/23 01:36 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/19 00:00 [pmc-release]
AID - ijms232416196 [pii]
AID - ijms-23-16196 [pii]
AID - 10.3390/ijms232416196 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 19;23(24):16196. doi: 10.3390/ijms232416196.