Pimenta Flávio Juliano, Gontijo Silveira Letícia Ferreira, Tavares Gabriela Cordeiro, Silva Andreza Campos, Perdigão Paolla Freitas, Castro Wagner Henriques, Gomez Marcus Vinícius, Teh Bin Tean, De Marco Luiz, Gomez Ricardo Santiago
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Brazil.
Oral Oncol. 2006 Aug;42(7):735-9. doi: 10.1016/j.oraloncology.2005.11.019. Epub 2006 Feb 2.
Ossifying fibroma (OF) is a benign neoplasm related to bone characterized by a progressive enlargement of the affected jaw. Recently, the candidate tumor suppressor gene HRPT2 was identified and alterations in this gene were related with the Hyperparathyroidism-jaw tumor syndrome that is characterized by parathyroid adenoma or carcinoma, fibro-osseous lesions (mainly OF) of the jaws, and renal lesions. The purpose of the present study was to evaluate the HRPT2 gene in OF. Tumour and blood samples were obtained from 3 patients with OF and one with juvenile ossifying fibroma (JOF). The results demonstrated three novel mutations in two out of three genotyped OF's. Interestingly, one of these patients showed a germ-line mutation after blood analysis. RT-PCR amplification was performed to analyze HRPT2 mRNA expression and only wild-type HRPT2 transcript was found in all tumours. Investigation of the parafibromin protein by immunohistochemistry showed a similar pattern of immunolocalization with strong nuclear and cytoplasmic staining in all cases. In conclusion, the present study shows for the first time mutations of HRPT2 gene in OF and suggests that OF may arise due to haploinsufficiency of the HRPT2 gene.
骨化性纤维瘤（OF）是一种与骨相关的良性肿瘤，其特征为患侧颌骨进行性增大。最近，候选抑癌基因HRPT2被鉴定出来，该基因的改变与甲状旁腺功能亢进-颌骨肿瘤综合征相关，该综合征的特征为甲状旁腺腺瘤或癌、颌骨的纤维-骨病变（主要是OF）以及肾脏病变。本研究的目的是评估OF中的HRPT2基因。从3例OF患者和1例青少年骨化性纤维瘤（JOF）患者获取肿瘤和血液样本。结果显示，在3例基因分型的OF中有2例出现了3种新的突变。有趣的是，其中1例患者血液分析后显示存在种系突变。进行逆转录聚合酶链反应（RT-PCR）扩增以分析HRPT2 mRNA表达，结果在所有肿瘤中仅发现野生型HRPT2转录本。通过免疫组织化学对 parafibromin 蛋白进行研究，结果显示在所有病例中免疫定位模式相似，均有强烈的核染色和胞质染色。总之，本研究首次显示了OF中HRPT2基因的突变，并提示OF可能是由于HRPT2基因单倍体不足所致。
