在上皮性神经母细胞瘤中TRIM28的失活是常见的,并且通常与易受TRIM28生殖系变异的诱导有关
Jenny Wegert1, Anne Kristin Fischer2, Balazs Palhazi1
1Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany.
The Journal of pathology
|October 4, 2023
概括
三方基因含有28 (TRIM28) 基因失活在上皮维尔姆斯瘤 (WTs) 中很常见,通常表明易感性. 在诊断中进行TRIM28测试可能会改善WT儿童的管理.
科学领域:
- 儿科瘤学 儿科瘤学
- 癌症遗传学 癌症遗传学
- 分子病理学分子病理学
背景情况:
- 威尔姆斯瘤 (WTs) 是具有不同组织学的儿童癌.
- 三方基因含有28 (TRIM28) 基因与WT发育有关.
- 之前的研究表明TRIM28突变与上皮WT亚型和倾向有关.
研究的目的:
- 调查TRIM28无活化和倾向性突变在上皮WTs的大队伍中的患病率.
- 描述TRIM28突变WTs的分子特征和临床表现.
- 评估TRIM28测试在WT管理中的诊断实用性.
主要方法:
- 在126个上皮质WTs中,针对TRIM28损失进行免疫组织化学染色.
- 对TRIM28序列变异 (同卵性/异卵性) 和表观遗传沉默的分子分析.
- 用表达式分析来定义分子亚型.
- 分析周边神经质休息物和患者生殖基因DNA.
主要成果:
- 在44.4%的WTs中检测到TRIM28损失;48个病例显示TRIM28序列变异 (双无活化).
- 突变主要是导致过早停止的密码体或移,影响蛋白质结构.
- TRIM28突变WTs形成了同质的上皮子集,通常是I阶段,缺乏典型的IGF2变化.
- 在46%的病例中,在生殖系/马赛克中发现了具有特征的TRIM28变异;前体病变含有相同的变化.
结论:
- TRIM28无活化是表皮性WTs中经常发生的事件,经常与生殖线倾向有关.
- TRIM28突变WTs代表了一个独特的分子亚型.
- 建议将TRIM28免疫组织化学整合到诊断中,以识别易受影响的儿童并量身定制治疗.
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