气候变化领域集成服务门户(CCPortal): Selection of metastasis competent subclones in the tumour interior

CCPortal

DOI	10.1038/s41559-021-01456-6
	Selection of metastasis competent subclones in the tumour interior
	Zhao Y.; Fu X.; Lopez J.I.; Rowan A.; Au L.; Fendler A.; Hazell S.; Xu H.; Horswell S.; Shepherd S.T.C.; Spain L.; Byrne F.; Stamp G.; O’Brien T.; Nicol D.; Augustine M.; Chandra A.; Rudman S.; Toncheva A.; Pickering L.; Sahai E.; Larkin J.; Bates P.A.; Swanton C.; Turajlic S.; Challacombe B.; Chowdhury S.; Drake W.; Fernando A.; Fotiadis N.; Furness A.; Hatipoglu E.; Harrison-Phipps K.; Hill P.; Horsfield C.; Marafioti T.; Olsburgh J.; Polson A.; Quezada S.; Varia M.; Verma H.; Litchfield K.; TRACERx Renal Consortium
发表日期	2021
ISSN	2397-334X
起始页码	1033
结束页码	1045
卷号	5 期号:7
英文摘要	The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates. We then integrated coordinates with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. We observed a phenotype of advanced and more aggressive subclonal growth in the tumour centre, characterized by an elevated burden of somatic copy number alterations and higher necrosis, proliferation rate and Fuhrman grade. Moreover, we found that metastasizing subclones preferentially originate from the tumour centre. Collectively, these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to a greater opportunity for driver somatic copy number alterations to arise and expand due to selective advantage. Tumour subclone growth is predominantly spatially contiguous in nature. We found only two cases of subclone dispersal, one of which was associated with metastasis. The largest subclones spatially were dominated by driver somatic copy number alterations, suggesting that a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution. ? 2021, The Author(s), under exclusive licence to Springer Nature Limited.
语种	英语
scopus关键词	copy number variation; genomics; human; molecular evolution; mutation; neoplasm; DNA Copy Number Variations; Evolution, Molecular; Genomics; Humans; Mutation; Neoplasms
来源期刊	Nature Ecology & Evolution
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/256908
作者单位	Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Biomolecular Modelling Laboratory, The Francis Crick Institute, London, United Kingdom; Department of Pathology, Cruces University Hospital, Biocruces-Bizkaia Institute, Barakaldo, Spain; Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom; Renal and Skin Unit, the Royal Marsden NHS Foundation Trust, London, United Kingdom; Department of Pathology, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, United States; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, Lon...
推荐引用方式 GB/T 7714	Zhao Y.,Fu X.,Lopez J.I.,et al. Selection of metastasis competent subclones in the tumour interior[J],2021,5(7).
APA	Zhao Y..,Fu X..,Lopez J.I..,Rowan A..,Au L..,...&TRACERx Renal Consortium.(2021).Selection of metastasis competent subclones in the tumour interior.Nature Ecology & Evolution,5(7).
MLA	Zhao Y.,et al."Selection of metastasis competent subclones in the tumour interior".Nature Ecology & Evolution 5.7(2021).