Suppr超能文献

Wilms 瘤的胚胎前体。

Embryonal precursors of Wilms tumor.

机构信息

Wellcome Sanger Institute, Hinxton CB10 1SA, UK.

Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.

出版信息

Science. 2019 Dec 6;366(6470):1247-1251. doi: 10.1126/science.aax1323.

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 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.

摘要

成人癌症通常起源于癌前克隆扩增。儿童肿瘤是否也是如此尚不清楚。为了研究Wilms 瘤(肾母细胞瘤;一种儿童肾癌)是否起源于癌前背景,我们研究了肿瘤与其相应正常组织之间的系统发生关系。在 23 例研究病例中的 14 例(61%)中,我们发现了在肿瘤发生之前存在于形态正常肾组织中的癌前克隆扩增。这些克隆扩增是由肿瘤和正常组织之间共享但不存在于血细胞中的体细胞突变定义的。我们还发现,在 58%的扩增中, 基因座的甲基化呈超甲基化状态,这是 Wilms 瘤发展的已知驱动因素。双侧肿瘤的系统发生分析表明,克隆扩增可以在左右肾原基分化之前发生进化。这些发现揭示了单侧和多灶性癌症的胚胎前体。

相似文献

1
Embryonal precursors of Wilms tumor.
Science. 2019 Dec 6;366(6470):1247-1251. doi: 10.1126/science.aax1323.
2
Microdissecting the genetic events in nephrogenic rests and Wilms' tumor development.
Am J Pathol. 1998 Sep;153(3):991-1000. doi: 10.1016/S0002-9440(10)65641-6.
3
4
A new precursor lesion of Wilms' tumour (nephroblastoma): intralobar multifocal nephroblastomatosis.
Histopathology. 1984 Jan;8(1):35-53. doi: 10.1111/j.1365-2559.1984.tb02320.x.
5
Evidence for clonal development of Wilms' tumor.
Am J Pediatr Hematol Oncol. 1991 Spring;13(1):26-8. doi: 10.1097/00043426-199121000-00006.
6
Origins of DNA methylation defects in Wilms tumors.
Cancer Lett. 2019 Aug 10;457:119-128. doi: 10.1016/j.canlet.2019.05.013. Epub 2019 May 16.
7
[Nephrogenic rests and nephroblastomatosis].
Ann Pathol. 2004 Dec;24(6):510-5. doi: 10.1016/s0242-6498(04)94015-1.
8
Allelotyping nephrogenic rests: putative precursor lesions of Wilms tumors.
Pediatr Dev Pathol. 1999 Sep-Oct;2(5):488-9. doi: 10.1007/s100249900154.

引用本文的文献

2
The Somatic Mosaicism across Human Tissues Network.
Nature. 2025 Jul;643(8070):47-59. doi: 10.1038/s41586-025-09096-7. Epub 2025 Jul 2.
3
4
Genes related to neural tube defects and glioblastoma.
Sci Rep. 2025 Jan 30;15(1):3777. doi: 10.1038/s41598-025-86891-2.
5
Predisposition Footprints in the Somatic Genome of Wilms Tumors.
Cancer Discov. 2025 Feb 7;15(2):286-298. doi: 10.1158/2159-8290.CD-24-0878.
6
Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors.
Nat Cancer. 2024 Nov;5(11):1681-1696. doi: 10.1038/s43018-024-00840-y. Epub 2024 Oct 15.
7
Defining precancer: a grand challenge for the cancer community.
Nat Rev Cancer. 2024 Nov;24(11):792-809. doi: 10.1038/s41568-024-00744-0. Epub 2024 Oct 1.
8
Multifocal, multiphenotypic tumours arising from an MTOR mutation acquired in early embryogenesis.
Oncogene. 2024 Oct;43(44):3268-3276. doi: 10.1038/s41388-024-03137-7. Epub 2024 Sep 13.
9
Pursuit of the optimal therapeutic approach and intensity for children with bilateral Wilms tumour.
Br J Cancer. 2024 Oct;131(6):970-971. doi: 10.1038/s41416-024-02806-4. Epub 2024 Aug 27.
10
Pediatric Tumors as Disorders of Development: The Case for In Vitro Modeling Based on Human Stem Cells.
Cancer Control. 2024 Jan-Dec;31:10732748241270564. doi: 10.1177/10732748241270564.

本文引用的文献

1
The mutational landscape of normal human endometrial epithelium.
Nature. 2020 Apr;580(7805):640-646. doi: 10.1038/s41586-020-2214-z. Epub 2020 Apr 22.
2
The landscape of somatic mutation in normal colorectal epithelial cells.
Nature. 2019 Oct;574(7779):532-537. doi: 10.1038/s41586-019-1672-7. Epub 2019 Oct 23.
3
Decoding human fetal liver haematopoiesis.
Nature. 2019 Oct;574(7778):365-371. doi: 10.1038/s41586-019-1652-y. Epub 2019 Oct 9.
4
The genetic changes of Wilms tumour.
Nat Rev Nephrol. 2019 Apr;15(4):240-251. doi: 10.1038/s41581-019-0112-0.
5
Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.
Science. 2018 Aug 10;361(6402):594-599. doi: 10.1126/science.aat1699.
7
Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.
Nature. 2017 Mar 30;543(7647):714-718. doi: 10.1038/nature21703. Epub 2017 Mar 22.
8
cgpCaVEManWrapper: Simple Execution of CaVEMan in Order to Detect Somatic Single Nucleotide Variants in NGS Data.
Curr Protoc Bioinformatics. 2016 Dec 8;56:15.10.1-15.10.18. doi: 10.1002/cpbi.20.
9
The contribution of branching morphogenesis to kidney development and disease.
Nat Rev Nephrol. 2016 Dec;12(12):754-767. doi: 10.1038/nrneph.2016.157. Epub 2016 Nov 7.
10
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
Nature. 2016 Jun 2;534(7605):47-54. doi: 10.1038/nature17676. Epub 2016 May 2.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验