<scp>DNA</scp> methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell‐rich histological mimics

Guimarães, Letícia Martins; Baumhoer, Daniel; Andrei, Vanghelita; Friedel, Dennis; Koelsche, Christian; Gomez, Ricardo Santiago; Deimling, Andreas von; Gomes, Carolina Cavaliéri

doi:10.1002/cjp2.337

Cited by 3 publications

(2 citation statements)

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“…The results of methylation classifiers must be interpreted by carefully correlating clinical, radiological, pathological, and genetic findings. We performed additional methylation classification after adding 71 cases of giant cell-rich bone tumors [15]. Although the present case was clustered with ABCs, non-ossifying fibromas were also intermingled.…”

Section: Discussionmentioning

confidence: 95%

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Nanopore DNA Sequencing Detected Chromothripsis‐Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma

Makise,

Lin,

Kageyama

et al. 2024

Genes Chromosomes & Cancer

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An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood‐filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high‐grade surface osteosarcoma. A 10‐year‐old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid–fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm2) and lace‐like osteoid formation, which was diagnosed as a high‐grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as “possibly osteoblastoma.” The patient was disease‐free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription‐polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non‐ossifying fibroma using t‐distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis.

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Section: Discussionmentioning

confidence: 95%

“…We further performed methylation clustering after adding Infinium data of 71 cases of giant cell-rich bone tumors (GSE218252) [15]. As a result, the present case was clustered with non-ossifying fibroma (NOF) and ABC, by means of t-SNE (Figure 2E) and unsupervised hierarchical clustering.…”

Section: Methylation Analysismentioning

confidence: 99%

Nanopore DNA Sequencing Detected Chromothripsis‐Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma

Makise,

Lin,

Kageyama

et al. 2024

Genes Chromosomes & Cancer

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Giant Cell-Rich Tumors of the Skeleton

Diaz-Perez,

Rosenberg

2024

Advances in Anatomic Pathology

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The accurate diagnosis of giant cell-rich tumors of bone is challenging, especially in limited tissue samples. This diverse group of neoplasms have similar and often ambiguous clinical presentations, radiologic features, and morphologic characteristics. During the last decade, the discovery of pathogenic recurrent genetic alterations has allowed the development of immunohistochemical surrogate markers and FISH assays that can help differentiate the entities of this broad group from one another. The correct diagnosis of these neoplasms is essential in the management of the affected patients.

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Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature

Kleijn,

Ameline,

Schreuder

et al. 2024

American Journal of Surgical Pathology

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Odontogenic myxoma is a rare, benign, and locally aggressive tumor that develops in the tooth-bearing areas of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available to date. The aim of this study was to analyze DNA methylation and copy number variations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making. We collected a cohort of 16 odontogenic myxomas from 2006 to 2021 located in the mandible (n = 10) and maxilla (n = 6) with available formalin-fixed paraffin-embedded or fresh frozen tumor tissue from a biopsy or resection material. Genome-wide DNA methylation and copy number variation data were generated from 12 odontogenic myxomas using the Illumina Infinium Methylation EPIC array, interrogating >850,000 CpG sites. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that odontogenic myxomas formed a distinct DNA methylation class. Copy number profiling showed recurrent whole-chromosome gains (trisomies) of chromosomes 5, 8, and 20 in all cases, and of chromosomes 10, 12, and 17 in all except one case. In conclusion, odontogenic myxomas harbor recurrent copy number patterns and a distinct DNA methylation profile, which can be used as an additional diagnostic tool in the appropriate clinical and radiologic context. Further research is needed to explain the genetic mechanisms caused by these alterations that drive these locally aggressive neoplasms.

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DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell‐rich histological mimics

Cited by 3 publications

References 38 publications

Nanopore DNA Sequencing Detected Chromothripsis‐Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma

Nanopore DNA Sequencing Detected Chromothripsis‐Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma

Giant Cell-Rich Tumors of the Skeleton

Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature

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