近日，英国威康桑格研究所Sam Behjati及其研究组发现了威尔姆斯肿瘤的胚胎前体。这一研究成果2019年12月6日发表在国际学术期刊《科学》上。
为了研究威尔姆斯肿瘤（肾母细胞瘤；一种儿童肾癌）是否从恶变前背景发展而来，研究人员剖析了肿瘤与相应正常组织之间的系统发育关系。在研究的23个病例中有14例（61％），研究人员在肿瘤发展之前形态正常的肾脏组织中发现了恶变前的扩张。这些克隆性扩增是由肿瘤和正常组织之间共有但血细胞中不存在的体细胞突变所定义的。研究人员还发现了58％的扩增中H19位点的高甲基化，这一位点是威尔姆斯肿瘤发展的已知驱动因素。对双侧肿瘤的系统发育分析表明，克隆扩张可以在左肾原基和右肾原基发散之前发展。这些发现揭示了单侧和多灶性癌症发展的胚胎前体。
据悉，成人癌症通常由恶变前的克隆扩张引起。目前尚不清楚儿童肿瘤是否同样如此。
附：英文原文
Title: Embryonal precursors of Wilms tumor
Author: Tim H. H. Coorens, Taryn D. Treger, Reem Al-Saadi, Luiza Moore, Maxine G. B. Tran, Thomas J. Mitchell, Suzanne Tugnait, Christine Thevanesan, Matthew D. Young, Thomas R. W. Oliver, Minou Oostveen, Grace Collord, Patrick S. Tarpey, Alex Cagan, Yvette Hooks, Mark Brougham, Ben C. Reynolds, Giuseppe Barone, John Anderson, Mette Jorgensen, G. A. Amos Burke, Johannes Visser, James C. Nicholson, Naima Smeulders, Imran Mushtaq, Grant D. Stewart, Peter J. Campbell, David C. Wedge, Iigo Martincorena, Dyanne Rampling, Liz Hook, Anne Y. Warren, Nicholas Coleman, Tanzina Chowdhury, Neil Sebire, Jarno Drost, Kourosh Saeb-Parsy, Michael R. Stratton, Karin Straathof, Kathy Pritchard-Jones, Sam Behjati
Issue&Volume: 2019/12/06
Abstract: Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.
DOI: 10.1126/science.aax1323
Source:https://science.sciencemag.org/content/366/6470/1247