EGAGenomicsIllumina HiSeq 2000, ILLUMINA, Illumina HiSeq 2500Otherhttps://ega-archive.org/studies/EGAS00001002102EGAEGA study EGAS00001002102Whole genome sequencing of 63 single cells isolated from bone marrow aspirates of six non-metastatic breast cancer patients after staining for disseminated tumor cells.Whole exome sequencing of bulk primary tumor (and one lymph node metastasis) and matched blood of six non-metastatic breast cancer patientsrestrictedEGAprimary breast cancer, malignant tumor of the breast, d230, Neoplasms, Benign Neoplasm, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, dTAFII250, Tumor, Malignant, EfW1, 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, Malignancy, cel, Mammary Neoplasm, cell, Mammary Carcinoma, Human Mammary Carcinomas, Taf1p, Cancer of the Breast, Neoplasias, dTAF250, cancer of breast, Malignant Tumor of Breast, Mammary, Mammary Cancer, Malignancies, Breast, mammary cancer, TAF, mammary tumor, Breast Malignant Neoplasms, Cancer, Tumors, Breast Carcinoma, Human Mammary Neoplasm, Carcinoma, dTAF[[II]]230, TAF[[II]]250, Breast Carcinomas, Malignant Neoplasm, "breast neoplasm" EXACT [MTH:120], TAF200, l(3)84Ab, BG:DS00004.13, TAFII-250, "breast tumor" EXACT [NCI2004_11_17:C2910], TAF250/230, Cell, dTAF230, Breast Malignant Neoplasm, TAFII250, Benign, Mammary Carcinomas, p230, Neoplasm, TAF[[II]]250/230, Human Mammary Carcinoma, TFIID, NOS, Malignant Neoplasm of Breast, Carcinomas, Taf[[II]]250, Breast Neoplasm, TAF[[II]]230, Benign Neoplasms, TAF[II]250, Cancers, "mammary neoplasm" RELATED [], CG17603, TAF[[II]], Malignant Neoplasms, DmelCG17603, TAF1., breast cancer, Taf250, SR3-5, Breast Tumors, Breast Cancer, Breast Malignant Tumors, Cancer of Breast, other neoplasm, cancer, Neoplasia, breast, TAF230Bones and Bone Tissue, malignant tumor of the breast, determination, Metastasis, Period Prevalence, Lymph Node Metastases, mammary neoplasm, Human Mammary Neoplasms, CG9842, Tumor, Long Term, osteogenic tissue, dmTAF[[II]]230, School-Age, Point Prevalence, Bone and Bone, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], medulla ossea, Point Prevalences, CAN A1/PP2B, 2900074D19Rik, CG1455, cancer of the breast, Effect, Calna, Bone Tissues, treatment, BC, CnnA14D, Mammary Neoplasms, malignant neoplasm of breast, thymus nucleic acid, TFIID TAF250, Genomes, cel, Prevalences, Tissue, Human Mammary Carcinomas, Dietary Fiber, Red Marrow, canA, cancer of breast, CN, disease management, Red, Therapies, Condyles, Malignancies, Double-Stranded DNA, PP2B, deoxyribonucleic acids, DNAn, mammary cancer, INCURVATA 4, Bony Apophyses, Breast Malignant Neoplasms, Long-Term Effects, Cana1, Tumors, Therapy, Carcinoma, Prevalence, dTAF[[II]]230, DmelCG1455, anatomical protrusion, "breast neoplasm" EXACT [MTH:120], aberrant, frequency, TAF200, Longterm Effect, Double-Stranded, TAFII-250, TAF250/230, results, Caln, (Deoxyribonucleotide)n+m, TAFII250, DmelCG9842, Benign, epithelial, School Age, RENBP, NOS, desoxyribose nucleic acid, Malignant Neoplasm of Breast, Carcinomas, Populations, medulla of bone, portion of bone tissue, Heterogeneity, Benign Neoplasms, Condyle, "mammary neoplasm" RELATED [], CG17603, TAF[[II]], surveillance, Treatments, DmCanA1-100B, morbidity, PP2B-14D, Malignant Neoplasms, AGE, metastatic, Bony, Taf250, breast cancer, Patient, bone, spine, SR3-5, Breast Tumors, ds DNA, Breast Malignant Tumors, School-Age Population, Bony Apophysis, DNA, other neoplasm, cancer, Bone, TAF230, ATHB15, Malignant Neoplasms., primary breast cancer, atypia, d230, DNS, (Deoxyribonucleotide)n, Effects, Neoplasms, Benign Neoplasm, number, Mammary Cancers, dTAFII250, Period Prevalences, CnA, EfW1, Malignant, presence, Deoxyribonucleic acids, PpD33, Human, protrusion, Breast Malignant Tumor, Deoxyribonucleic Acid, dmTAF1, Taf230, Breast Tumor, Pp2B-14DF, Marrow, Core Genome, Genetic heterogeneity, "mammary tumor" EXACT [CSP2005:2016-0671], breast tumor, Yellow, atypical, CNA, ICU4, TAF250, CnnA21EF, study, School-Age Populations, Taf200, Human Mammary, dTAF[[II]]250, Genetic, Genetic Heterogeneities, Malignancy, occurrence, Longterm, cell, Tissues, Mammary Neoplasm, Mammary Carcinoma, Accessory Genome, prevalence, Double Stranded, Taf1p, Deoxyribonucleic acid, Long-Term, Population, Cancer of the Breast, Neoplasias, dTAF250, AW413465, D14, 10^[-6], Malignant Tumor of Breast, Mammary, Mammary Cancer, Clients, Apophysis, Long-Term Effect, (Deoxyribonucleotide)m, School Age Population, TAF, Breast, mammary tumor, incidence, Pp12-14D, Cancer, Breast Carcinoma, Human Mammary Neoplasm, TAF[[II]]250, Breast Carcinomas, Malignant Neoplasm, Apophyses, AI841391, DmPp2B-14D, RnBP, DNAn+1, GlcNAc 2-epimerase, l(3)84Ab, Lymph Node Metastasis, BG:DS00004.13, defective, "breast tumor" EXACT [NCI2004_11_17:C2910], Pangenome, Client, Cell, dTAF230, Bones and Bone, Breast Malignant Neoplasm, CanA14D, count in organism, CNA1, D33, N-acetyl-D-glucosamine 2-epimerase, medulla ossium, Period, Mammary Carcinomas, p230, pMY4, chemical analysis, Long Term Effects, Neoplasm, TAF[[II]]250/230, sequence, Can, TFIID, Human Mammary Carcinoma, background, bones, ds-DNA, outbreaks, epitheliocyte, Taf[[II]]250, PP2B 21EF, Yellow Marrow, osseous tissue, Breast Neoplasm, TAF[[II]]230, CORONA, Lymph Node, medullary bone, F5F19.21, Heterogeneities, TAF[II]250, Lymphatic Metastases, Cancers, Bones, PpD14, School Age Populations, primary structure of sequence macromolecule, endemics, introduction, Longterm Effects, F5F19_21, PP2B 14D, DmelCG17603, mineralized bone tissue, Pan-genome, Therapeutic, Bone Tissue, Point, Breast Cancer, cardinality, Desoxyribonukleinsaeure, renin-binding protein, Treatment, calcium tissue, Cancer of Breast, epidemics, assay, bone organ, Neoplasia, breast, TAF1falseTracing the origin of disseminated tumor cells in breast cancer using single-cell sequencingBackground Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. Results We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant ‘normal’ cells or aberrant cells of unknown origin that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent, and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis. Conclusions Single-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.2017-07-26 15:39:29EGAS000010021029606EGAD00001002746EGAD00001002745EGAC00001000558