Fibro-osseous tumors and dysplasias

2025-11-24   Paola Dal Cin, PhD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Keywords
GNAS mutations; MDM2 and RASL1 co-amplification;SATB2 rearrangement

Classification

Definition

Bone and cartilage tumors Genetic markers
Fibro-osseous tumors and dysplasias
Cemento-osseous dysplasia (COD)They are the most common fibro-osseous lesion in the jaws ,developing exclusively in the tooth-bearing areas of the gnathic bones. Pathogenic hotspot mutations involving the RAS-MAPK signalling pathway were detected e.g., BRAF, HRAS, KRAS, NRAS, and FGFR3 mutations. 1
Segmental odontomaxillary dysplasia (SOD)A non-hereditary, unilateral developmental anomaly, typically manifests in early childhood, with a male predominance and associated with PIK3CA or ACTB mutations.2,3
Fibrous dysplasia (FD)GNAS mutations at codon 201 , most commonly p.(Arg201His) or p.(Arg201Cys), resulting in the constitutive activation of Wnt/b-catenin signaling pathway can be identified in FD cases and are not present in other fibro-osseous lesions.4 They can occurr sporadically or in association with McCune-Albright syndrome OMIM:174800, Jeffe-Lichenstein syndrome OMIM:246550 or Mazabraud syndrome,5
Juvenile trabecular ossifying fibroma (JTOF)To date JTOF represents a heterogeneous group of tumors at the genetic level: 1) Recurrent MDM2 and RASL1 amplification were reported ,6 but not reportes by others, 7 2) subset of cases shows CDC73 mutations and recurrent gene copy number gain/amplification of TBX3,FOS, FOSB and COL1A1,8 and a single JTOF case of with SATB2::EXOC6B fusion , probably from a pericentric inversion from between EXOC6B ad 2p13.1 and SATB2 at 2q 33.1, with concurrent deletion of exons in both genes. 9
Psammomatoid ossifying fibroma (PsOF)Psammomatoid ossifying fibroma (PsOF), also known as juvenile PsOF, is associated with SATB2 rearrangement at 2q33.1,10 with SATB2::AL513487 fusion,associated with t(X;2)(q26;q33) seen by karyotyping . 11 A single case with both PsOF and secondary ABC like changes exhibited a frameshift SETD2 somatic mutation at 3p21.31. 12
Familial gigantiform cementomaFamilial gigantiform cementoma can be inherited in an autosomal dominant fashion and is also described in rare generalized skeleton syndromes like gnathodiaphyseal dysplasia (GDD) OMIM:166260, carrying ANO5 mutation. 13

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1367073182023Cemento-osseous dysplasia is caused by RAS-MAPK activation.Haefliger S et al
2325004252021Segmental Ipsilateral Odontognathic Dysplasia (Mandibular Involvement in Segmental Odontomaxillary Dysplasia?) and Identification of PIK3CA Somatic Variant in Lesional Mandibular Gingival Tissue.Gibson TM et al
3397763782025Segmental Odontomaxillary Dysplasia: Unusual Tumoral Lesion.de Lima Castro FLA et al
4303761902019Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical, radiological, and histopathological features.Pereira TDSF et al
5359748902022Mazabraud's Syndrome.Adrien M et al
6249250562015Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions.Tabareau-Delalande F et al
735546651987Immunogenicity of the non-MHC-encoded endothelial antigen Eag-1 in various tissues of the rat.Blankert JJ et al
8369287412023Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing.Bahceci DH et al
9388907842024SATB2-rearrangement in a case of juvenile trabecular ossifying fibroma, expanding the spectrum of SATB2-rearranged neoplasia.Perret R et al
10367880652023Psammomatoid Ossifying Fibroma Is Defined by SATB2 Rearrangement.Cleven AHG et al
1186250581995Nonrandom chromosome breakpoints at Xq26 and 2q33 characterize cemento-ossifying fibromas of the orbit.Sawyer JR et al
12346576062021First presentation of a frameshift mutation in the SETD2 gene of a juvenile psammomatoid ossifying fibroma (JPOF) associated with an aneurysmal bone cyst.Toferer A et al
13272169122016Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.Andreeva TV et al

Citation

Paola Dal Cin, PhD

Fibro-osseous tumors and dysplasias

Atlas Genet Cytogenet Oncol Haematol. 2025-11-24

Online version: http://atlasgeneticsoncology.org/solid-tumor/209347/fibro-osseous-tumors-and-dysplasias