Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025
Classification of Fibro-Osseous Tumors in the Craniofacial Bones Using DNA Methylation and Copy Number Alterations.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Kleijn Tony G, Ameline Baptiste, Schreuder Willem H, Szuhai Károly, Kooistra Wierd, van Kempen Léon, Japalagh Ghazaleh S H, Briaire-de Bruijn Inge H, van der Meeren Stijn W, Kleijwegt Maarten C, Witjes Max, Pichardo Sarina E C, van Furth Wouter R, Lausová Tereza, Breimer Gerben E, Braunius Weibel, de Lange Jan, van Langevelde Kirsten, Kroon Herman M, van den Hout Mari F C M, Koppes Sjors A, Haefliger Simon, Ooft Marc L, van Engen-van Grunsven Ilse C H, Flucke Uta E, Hiemcke-Jiwa Laura, Savci-Heijink Dilara C, Diercks Gilles F H, Doff Jan J, Suurmeijer Albert J H, Bovée Judith V M G, von Deimling Andreas, Baumhoer Daniel, Cleven Arjen H G
Аннотация
Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS. Because DNA methylation and copy number profiling are well established for the classification of central nervous system tumors, we aimed to investigate whether this tool might be used as well for classifying fibro-osseous tumors in the craniofacial bones. We collected a well-characterized, multicenter cohort with available molecular data, including COD (n = 20), COF (n = 13), JTOF (n = 10), PsOF (n = 25), FD (n = 23), LGOS (n = 4), and high-grade osteosarcoma (HGOS; n = 11). Genome-wide DNA methylation and copy number variation data were generated using the Illumina Infinium Methylation EPIC array interrogating >850 000 CpG sites. DNA methylation profiling yielded evaluable results in 73/106 tumors, including 6 CODs, 12 COFs, 6 JTOFs, 19 PsOFs, 18 FDs, 2 LGOSs, and 10 HGOSs. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that FD, extragnatic PsOF, and HGOS formed distinct clusters. Surprisingly, COD, COF, JTOF, and mandibular PsOF clustered together, apart from other craniofacial bone tumors. LGOS did not form a distinct cluster, likely due to the low number of cases. Copy number analysis revealed that FD, COD, COF, JTOF, and PsOF were typically characterized by flat copy number profiles compared with LGOS with gains of chromosome 12 and HGOS with multiple heterogeneous copy number alterations. In conclusion, using DNA methylation and copy number profiles, benign fibro-osseous tumors can be separated from low-grade and HGOSs in the craniofacial bones, which is of diagnostic value in challenging cases with overlapping clinicopathological features.