Lietman Steven A, Prescott Nichole L, Hicks David G, Westra William H, Levine Michael A
Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
Clin Orthop Relat Res. 2007 Jun;459:22-7. doi: 10.1097/BLO.0b013e31804b4131.
Giant cell tumor of bone and giant cell reparative granuloma are benign lesions with prominent giant (multinucleated) cells, and an understanding of the molecular biology and genetics of these lesions will likely aid in more effective treatment. Cherubism is a benign lesion of the maxilla and mandible histologically similar to giant cell tumor of bone and giant cell reparative granuloma. Germline mutations in exon 9 of the gene encoding Src homology 3 binding protein 2 (SH3BP2) occur in most patients with cherubism. We therefore hypothesized SH3BP2 and its putative downstream effector nuclear factor of activated T cells c1 isoform (NFATc1) are highly expressed in sporadic nonsyndromic giant cell lesions and associated with somatic SH3BP2 mutations. We analyzed giant cell lesions for SH3BP2 and NFATc1 expression by RNA blot and/or immunohistochemistry and for exon 9 SH3BP2 mutations. We found the SH3BP2 transcripts and protein were abundantly expressed in giant cell tumors of bone, as well as NFATc1 protein. Sequencing of exon 9 of SH3BP2 was normal in all sporadic nonsyndromic giant cell lesions. Although many multinucleated giant cell lesions of bone share histologic features, the primary genetic defect in cherubism and these other giant cell lesions appears different.
骨巨细胞瘤和巨细胞修复性肉芽肿是具有显著巨细胞（多核细胞）的良性病变，了解这些病变的分子生物学和遗传学可能有助于更有效的治疗。 cherubism是一种上颌骨和下颌骨的良性病变，在组织学上与骨巨细胞瘤和巨细胞修复性肉芽肿相似。大多数cherubism患者存在编码Src同源3结合蛋白2（SH3BP2）的基因外显子9中的种系突变。因此，我们推测SH3BP2及其假定的下游效应物活化T细胞核因子c1异构体（NFATc1）在散发性非综合征性巨细胞病变中高度表达，并与体细胞SH3BP2突变相关。我们通过RNA印迹和/或免疫组织化学分析巨细胞病变中SH3BP2和NFATc1的表达，并分析SH3BP2外显子9的突变情况。我们发现SH3BP2转录本和蛋白在骨巨细胞瘤中大量表达，NFATc1蛋白也是如此。在所有散发性非综合征性巨细胞病变中，SH3BP2外显子9的测序均正常。尽管许多骨的多核巨细胞病变具有共同的组织学特征，但cherubism和其他巨细胞病变的主要遗传缺陷似乎不同。
