PDF(Pubmed)
Abstract：
Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).
摘要：
颌骨散发性巨细胞肉芽肿（GCGs）和与胆碱病相关的巨细胞病变具有组织病理学特征，仅进行显微镜诊断可能具有挑战性。此外,GCG在形态上与其他富含巨细胞的病变非常相似，包括非骨化性纤维瘤（NOF），动脉瘤样骨囊肿（ABC），骨巨细胞瘤（GCTB），和软骨母细胞瘤.这些富含巨细胞的肿瘤的表观遗传学基础尚不清楚，DNA甲基化谱已被证明在临床上可用于其他肿瘤类型的诊断。因此,我们的目的是评估中枢和外周散发性GCG和天使症的DNA甲基化谱,以检验DNA甲基化模式是否有助于区分它们.此外,我们将这些病变的DNA甲基化谱与其他富含巨细胞的模拟物进行了比较,以研究微观相似性是否延伸到表观遗传水平.对中枢（n=10）和外周（n=10）GCG进行DNA甲基化分析，天使主义（n=6），NOF(n=10),ABC（n=16），GCTB（n=9），和软骨母细胞瘤(n=10)使用Infinium人甲基化EPIC芯片。中枢和外周散发性GCG和天使症共享相关的DNA甲基化模式，与那些周围的GCG和天使出现轻微明显，而中央GCG显示与前者重叠。NOF,ABC,GCTB,软骨母细胞瘤，另一方面,有不同的甲基化模式。总体和增强子相关的CpGDNA甲基化值在中枢和外周GCG和cherubism之间显示出相似的分布模式，天党病显示最低，外周GCG中位数最高。相比之下,启动子区域显示不同的甲基化分布模式，天使主义的中位数最高。总之,DNA甲基化分析目前无法清楚地区分散发性和与小天使相关的巨细胞病变。相反，它可以将颌骨的零星GCG与它们富含巨细胞的模仿物区分开(NOF，ABC,GCTB,和软骨母细胞瘤）。
