EGAGenomicsIllumina MiSeq;, Illumina HiSeq 2000;https://ega-archive.org/datasets/EGAD00001001066188EGA dataset EGAD00001001066EGAHuman cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.Eirew Peter P, Steif Adi A, Khattra Jaswinder J, Ha Gavin G, Yap Damian D, Farahani Hossein H, Gelmon Karen K, Chia Stephen S, Mar Colin C, Wan Adrian A, Laks Emma E, Biele Justina J, Shumansky Karey K, Rosner Jamie J, McPherson Andrew A, Nielsen Cydney C, Roth Andrew J L AJ, Lefebvre Calvin C, Bashashati Ali A, de Souza Camila C, Siu Celia C, Aniba Radhouane R, Brimhall Jazmine J, Oloumi Arusha A, Osako Tomo T, Bruna Alejandra A, Sandoval Jose L JL, Algara Teresa T, Greenwood Wendy W, Leung Kaston K, Cheng Hongwei H, Xue Hui H, Wang Yuzhuo Y, Lin Dong D, Mungall Andrew J AJ, Moore Richard R, Zhao Yongjun Y, Lorette Julie J, Nguyen Long L, Huntsman David D, Eaves Connie J CJ, Hansen Carl C, Marra Marco A MA, Caldas Carlos C, Shah Sohrab P SP, Aparicio Samuel SVasp, VASP, 907, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, XXD, Data Set, 907 细胞, NICR1852., XD, Dhekelia, MENA, NDPP1, Eastern Sovereign Base Area, l(2)02029, Enb, enb, 907 cell, ENA, Ena, DHEKELIA, Dhekelia Sovereign Base Area, CG15112, ENA/VASPprimary breast cancer, malignant tumor of the breast, d230, Heterograft, Neoplasms, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, dTAFII250, TRANSPL HETEROL, Tumor, Transplantations, EfW1, heterologous transplantation, Human, dmTAF[[II]]230, Breast Malignant Tumor, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], dmTAF1, Breast Tumor, Taf230, "mammary tumor" EXACT [CSP2005:2016-0671], breast tumor, cancer of the breast, TAF250, BC, Mammary Neoplasms, malignant neoplasm of breast, Taf200, Human Mammary, dTAF[[II]]250, TFIID TAF250, cel, Mammary Neoplasm, cell, Mammary Carcinoma, Human Mammary Carcinomas, Heterografts, Taf1p, Cancer of the Breast, dTAF250, 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dTAF[[II]]230, TAF[[II]]250, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], TAF200, l(3)84Ab, BG:DS00004.13, TAFII-250, "breast tumor" EXACT [NCI2004_11_17:C2910], TAF250/230, Client, Cell, dTAF230, Breast Malignant Neoplasm, TAFII250, XENOTRANSPL, Mammary Carcinomas, p230, Neoplasm, TAF[[II]]250/230, Human Mammary Carcinoma, TFIID, NOS, Malignant Neoplasm of Breast, Heterologous Transplantations, Carcinomas, Taf[[II]]250, Xenograft, Breast Neoplasm, Xenotransplantation, TAF[[II]]230, Transplantation, HETEROL TRANSPL, patient, TAF[II]250, Cancers, Xenografts, "mammary neoplasm" RELATED [], CG17603, TAF[[II]], DmelCG17603, TAF1., breast cancer, Patient, Taf250, SR3-5, Breast Tumors, Breast Cancer, Breast Malignant Tumors, Cancer of Breast, cancer, breast, TAF230malignant tumor of the breast, Residential, Transitions, Breasts, degree (angle), Mobility, Metastasis, Laboratory, Heterograft, Stable Population, selection process, neoplasia, Mus domesticus, Lactiferous gland, mammary neoplasm, Human Mammary Neoplasms, Neoplasm Metastases, CASP-14, CSMF, neoplasm metastasis, TRANSPL HETEROL, Aging, Tumor, Graft, composed of, House Mouse, glandula mammaria, Long Term, cancer metastasis, Mutations, dmTAF[[II]]230, School-Age, Techniques, Decreases, Stationary, Population Pressures, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Method, Population Replacement, cancer of the breast, Effect, drug resistance, BC, Mammary Neoplasms, malignant neoplasm of breast, Theory, grafting, Man (Taxonomy), TFIID TAF250, Genomes, cel, cell process disease, tumor disease, neoplasm (disease), Tissue, Human Mammary Carcinomas, composition, Swiss Mice, procedures, Estimated, Tissue Graft, Tissue Transplant, Population Theory, NOR-1, Xenotransplantations, Methodological Studies, Cell Transplant, cancer of breast, tumor, Theories, mammary cancer, Long-Term Effects, Breast Malignant Neoplasms, Tissue Grafts, Tumors, mamma, Carcinoma, Organ Transplant, dTAF[[II]]230, 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Mice, Dynamics, TAF[II]250, patient, Cancers, arc degree, Breast Malignant Neoplasms., disease of cellular proliferation, School Age Populations, Organ Graft, Longterm Effects, Laboratory Mice, Drug, Genogroups, DmelCG17603, Population Pressure, Pressures, Modern Man, Breast Cancer, structure, Demographic Aging, Cancer of Breast, TEC, Laboratory Mouse, Minor, NEOPLASMS BENIGN, Neoplasia, breast, methodology, TAF1falseena-DATASET-BCCA-13-11-2014-22:09:20:907-954 - samplesDynamics of genomic clones in breast cancer patient xenografts at single cell resolution2017-07-26 15:39:26EGAD00001001066960625470049EGAC00000000011EGAS00001000952