Kang, H., Salomon, M. P., Sottoriva, A., Zhao, J. S., Toy, M., Press, M. F., Curtis, C., Marjoram, P., Siegmund, K., Shibata, D. (2015) Many private mutations originate from the first few divisions of a human colorectal adenoma. JOURNAL OF PATHOLOGY, 237 (3). pp. 355-362. ISSN 0022-3417

Full text not available from this repository.

Abstract

Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. Here we find that ITH can be remarkably well structured by measuring point mutations, chromosome copy numbers, and DNA passenger methylation from opposite sides and individual glands of a 6cm human colorectal adenoma. ITH was present between tumour sides and individual glands, but the private mutations were side-specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumour originates from the first few divisions. Much of the early history of a tumour, especially the first few divisions, may be embedded within the detectable ITH of tumour genomes. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Item Type:	Article
Authors (ICR Faculty only):	Sottoriva, Andrea
All Authors:	Kang, H., Salomon, M. P., Sottoriva, A., Zhao, J. S., Toy, M., Press, M. F., Curtis, C., Marjoram, P., Siegmund, K., Shibata, D.
Additional Information:	ISI Document Delivery No.: CU0MM Times Cited: 0 Cited Reference Count: 26 Kang, Haeyoun Salomon, Matthew P. Sottoriva, Andrea Zhao, Junsong Toy, Morgan Press, Michael F. Curtis, Christina Marjoram, Paul Siegmund, Kimberly Shibata, Darryl Nih [r21 ca185016, p30ca014089] This study was supported by grants from the NIH (R21 CA185016, P30CA014089). 0 1 Wiley-blackwell Hoboken 1096-9896
Uncontrolled Keywords:	colorectal adenoma intratumoural heterogeneity mutation topography Big Bang tumourigenesis 21 breast cancers intratumor heterogeneity genetic instability evolution consequences polyploidy history tissue apc Oncology Pathology
Research teams:	ICR divisions > Molecular Pathology > Centre for Evolution and Cancer ICR divisions > Molecular Pathology > Evolutionary Genomics and Modelling
Depositing User:	Franziska Noessig
Date Deposited:	16 Nov 2015 15:35
Last Modified:	16 Nov 2015 15:35
URI:	http://publications.icr.ac.uk/id/eprint/14525

Actions (login required)

View Item