在人类甲状腺癌中PAX8-PPARgamma1融合瘤基因[修正]
T G Kroll1, P Sarraf, L Pecciarini
1Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. tkroll@rics.bwh.harvard.edu
Science (New York, N.Y.)
|August 26, 2000
概括
在甲状腺卵泡癌中发现了一种新型的基因融合,PAX8-PPARgamma1,驱动癌症的发展. 这一发现为甲状腺癌提供了潜在的新诊断和治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 在白血病/淋巴瘤和肉瘤中,染色体转位产生融合coproteins是常见的.
- 这些转位在癌症中一直没有被观察到,这是人类最常见的癌症.
- 驱动甲状腺卵泡癌发展的特定遗传变化需要进一步阐明.
研究的目的:
- 为了研究人类甲状腺卵泡癌的一个子集背后的分子机制.
- 识别和描述与甲状腺癌相关的新型基因融合.
- 探索已识别的融合蛋白在瘤发生中的功能作用.
主要方法:
- 型分析以确定染色体转位.
- 反转录-聚合酶链反应 (RT-PCR) 检测聚变转录.
- 西方涂抹以确认聚变产品的蛋白质表达.
- 功能性测试,以评估融合蛋白对基因交换激活的影响.
主要成果:
- 在甲状腺毛囊癌中发现了一种特定的转位,t(2;3)(q13;p25).
- 这种转位导致PAX8-PPARgamma1融合基因的形成.
- PAX8-PPARgamma1 mRNA和蛋白质在研究的8种甲状腺卵泡癌中的5种中被检测到.
- 在良性甲状腺瘤和正常甲状腺组织中,没有融合蛋白.
- 在PAX8-PPARgamma1中,表现出对氧酶增殖器激活受体gamma1 (PPARgamma1) 活性的主导负抑制.
结论:
- PAX8-PPARgamma1融合瘤基因在甲状腺卵泡癌的发展中发挥着作用.
- 在这种情况下,氧体增殖器激活受体玛 (PPARgamma) 可能具有致癌功能.
- 该PAX8-PPARgamma1融合蛋白代表了甲状腺癌诊断的潜在生物标志物.
- 准PAX8-PPARgamma1融合可能为甲状腺癌治疗提供一种新的治疗策略.
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