PMID- 36788065
OWN - NLM
STAT- MEDLINE
DCOM- 20230216
LR  - 20230316
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 36
IP  - 1
DP  - 2023 Jan
TI  - Psammomatoid Ossifying Fibroma Is Defined by SATB2 Rearrangement.
PG  - 100013
LID - S0893-3952(22)00013-8 [pii]
LID - 10.1016/j.modpat.2022.100013 [doi]
AB  - Psammomatoid ossifying fibroma (PsOF), also known as juvenile PsOF, is a benign 
      fibro-osseous neoplasm predominantly affecting the extragnathic bones, 
      particularly the frontal and ethmoid bones, with a preference for adolescents and 
      young adults. The clinical and morphologic features of PsOF may overlap with 
      those of other fibro-osseous lesions, and additional molecular markers would help 
      increase diagnostic accuracy. Because identical chromosomal breakpoints at bands 
      Xq26 and 2q33 have been described in 3 cases of PsOF located in the orbita, we 
      aimed to identify the exact genes involved in these chromosomal breakpoints and 
      determine their frequency in PsOF using transcriptome sequencing and fluorescence 
      in situ hybridization (FISH). We performed whole RNA transcriptome sequencing on 
      frozen tissue in 2 PsOF index cases and identified a fusion transcript involving 
      SATB2, located on chromosome 2q33.1, and AL513487.1, located on chromosome Xq26, 
      in one of the cases. The fusion was validated using reverse transcription 
      (RT)-PCR and SATB2 FISH. The fusion lead to a truncated protein product losing 
      most of the functional domains. Subsequently, we analyzed an additional 24 
      juvenile PsOFs, 8 juvenile trabecular ossifying fibromas (JTOFs), and 11 
      cemento-ossifying fibromas (COFs) for SATB2 using FISH and found evidence of 
      SATB2 gene rearrangements in 58% (7 of 12) of the evaluable PsOF cases but not in 
      any of the evaluable JTOF (n = 7) and COF (n = 7) cases. A combination of SATB2 
      immunofluorescence and a 2-color SATB2 FISH in our index case revealed that most 
      tumor cells harboring the rearrangement lacked SATB2 expression. Using 
      immunohistochemistry, 65% of PsOF, 100% of JTOF, and 100% of COF cases showed 
      moderate or strong staining for SATB2. In these cases, we observed a mosaic 
      pattern of expression with >25% of the spindle cells in between the bone matrix, 
      with osteoblasts and osteocytes being positive for SATB2. Interestingly, 35% (8 
      of 23) of PsOFs, in contrast to JTOFs and COFs, showed SATB2 expression in <5% of 
      cells. To our knowledge, this is the first report that shows the involvement of 
      SATB2 in the development of a neoplastic lesion. In this study, we have showed 
      that SATB2 rearrangement is a recurrent molecular alteration that appears to be 
      highly specific for PsOF. Our findings support that PsOF is not only 
      morphologically and clinically but also genetically distinct from JTOF and COF.
CI  - Copyright (c) 2022 United States & Canadian Academy of Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Cleven, Arjen H G
AU  - Cleven AHG
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands; Department of Pathology and Medical Biology, University Medical 
      Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic 
      address: a.h.g.cleven@lumc.nl.
FAU - Szuhai, Karoly
AU  - Szuhai K
AD  - Department of Cell and Chemical Biology, Leiden University Medical Center, 
      Leiden, the Netherlands.
FAU - van IJzendoorn, David G P
AU  - van IJzendoorn DGP
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands; Department of Pathology, Stanford University, Stanford, California.
FAU - Groen, Eline
AU  - Groen E
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Baelde, Hans
AU  - Baelde H
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Schreuder, Willem H
AU  - Schreuder WH
AD  - Department of Oral and Maxillofacial Surgery/Head and Neck Surgery, Amsterdam 
      University Medical Center/Antoni van Leeuwenhoek Hospital, Amsterdam, the 
      Netherlands.
FAU - Briaire-de Bruijn, Inge H
AU  - Briaire-de Bruijn IH
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - van der Meeren, Stijn W
AU  - van der Meeren SW
AD  - Department of Ophthalmology, Leiden University Medical Center, Leiden, the 
      Netherlands; Department of Ophthalmology, Amsterdam University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Kleijwegt, Maarten C
AU  - Kleijwegt MC
AD  - Department Head and Neck Surgery, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Furth, Wouter R
AU  - Furth WR
AD  - Department of Neurosurgery, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Kroon, Herman M
AU  - Kroon HM
AD  - Department of Radiology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Suurmeijer, Albert J H
AU  - Suurmeijer AJH
AD  - Department of Pathology and Medical Biology, University Medical Center Groningen, 
      University of Groningen, Groningen, the Netherlands.
FAU - Savci-Heijink, Dilara C
AU  - Savci-Heijink DC
AD  - Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
FAU - Baumhoer, Daniel
AU  - Baumhoer D
AD  - Bone Tumour Reference Centre, Institute of Medical Genetics and Pathology, 
      University Hospital Basel, University of Basel, Basel, Switzerland.
FAU - Bovee, Judith V M G
AU  - Bovee JVMG
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (SATB2 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Matrix Attachment Region Binding Proteins)
SB  - IM
MH  - Humans
MH  - *Fibroma, Ossifying/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - *Bone Neoplasms/genetics
MH  - Immunohistochemistry
MH  - Gene Rearrangement
MH  - Transcription Factors/genetics
MH  - *Matrix Attachment Region Binding Proteins/genetics
OTO - NOTNLM
OT  - SATB2
OT  - juvenile psammomatoid ossifying fibroma
OT  - psammomatoid ossifying fibroma
EDAT- 2023/02/15 06:00
MHDA- 2023/02/17 06:00
CRDT- 2023/02/14 22:04
PHST- 2022/04/11 00:00 [received]
PHST- 2022/09/12 00:00 [revised]
PHST- 2022/09/16 00:00 [accepted]
PHST- 2023/02/14 22:04 [entrez]
PHST- 2023/02/15 06:00 [pubmed]
PHST- 2023/02/17 06:00 [medline]
AID - S0893-3952(22)00013-8 [pii]
AID - 10.1016/j.modpat.2022.100013 [doi]
PST - ppublish
SO  - Mod Pathol. 2023 Jan;36(1):100013. doi: 10.1016/j.modpat.2022.100013.