Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Brazil.
J Oral Pathol Med. 2010 Mar;39(3):269-74. doi: 10.1111/j.1600-0714.2009.00855.x. Epub 2009 Dec 11.
Activation mutations of SH3BP2 gene have been demonstrated in cherubism and central giant cell lesion (CGCL). In the present study we first attempted to investigate the SH3BP2 gene in peripheral giant cell lesion (PGCL). The effect of SH3BP2 gene mutations on the transcription of the downstream genes nuclear factor of activated T cells (NFATc1) and the cytokine tumor necrosis factor-alpha (TNF-alpha) was also investigated together with the immunolocalization of NFATc1 protein in a set of cases of PGCL, CGCL and cherubism with and without SH3BP2 mutation.
Fresh samples of five PGCL, five CGCL and one cherubism cases were included in this study. One of the samples of CGCL presented a somatic heterozygous mutation c.1442A>T in exon 11. The cherubism case showed a heterozygotic substitution c.320C>T in both blood and lesion. These mutations were previously published. All coding and flanking regions of the SH3BP2 gene were sequenced in the cases of PGCL. The real-time polymerase chain reaction (RT-PCR) was performed to analyze the transcription of NFATc1 and TNF-alpha genes. The immunohistochemical analysis of the NFATc1 protein was also performed.
No SH3BP2 gene mutation was found in PGCL. The RT-PCR showed increased expression of NFATc1 and decreased transcription of TNF-alpha in all the samples. The immunohistochemical analysis of the NFATc1 protein showed a predominant nuclear staining in the multinucleated giant cells.
The development of giant cells lesions of the jaws and cherubism are possibly mediated by overexpression of NFAT in the nucleus of the multinucleated cells.
SH3BP2 基因突变已在 cherubism 和中央性 giant cell 病变（CGCL）中得到证实。本研究首次尝试研究下颌骨外周性 giant cell 病变（PGCL）中的 SH3BP2 基因。还研究了 SH3BP2 基因突变对下游基因核因子活化 T 细胞（NFATc1）和细胞因子肿瘤坏死因子-α（TNF-α）转录的影响，并对一组伴有和不伴有 SH3BP2 突变的 PGCL、CGCL 和 cherubism 病例进行了 NFATc1 蛋白的免疫定位。
本研究纳入了 5 例 PGCL、5 例 CGCL 和 1 例 cherubism 新鲜样本。其中 1 例 CGCL 样本在第 11 外显子中存在体细胞杂合突变 c.1442A>T。 cherubism 病例在血液和病变中均显示杂合性替换 c.320C>T。这些突变先前已有报道。对 PGCL 病例的 SH3BP2 基因所有编码和侧翼区域进行测序。进行实时聚合酶链反应（RT-PCR）分析 NFATc1 和 TNF-α 基因的转录。还进行了 NFATc1 蛋白的免疫组织化学分析。
PGCL 中未发现 SH3BP2 基因突变。RT-PCR 显示所有样本中 NFATc1 表达增加，TNF-α 转录减少。NFATc1 蛋白的免疫组织化学分析显示多核巨细胞中存在主要的核染色。
颌骨 giant cell 病变和 cherubism 的发展可能是通过多核细胞核中 NFAT 的过度表达介导的。
