title: Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer.
abstract: Chromosomal instability in human breast cancer is known to take place before mammary neoplasias display morphological signs of invasion. We describe here the unexpected finding of a tumor cell population with normal karyotypes isolated from bone marrow of breast cancer patients. By analyzing the same single cells for chromosomal aberrations, subchromosomal allelic losses, and gene amplifications, we confirmed their malignant origin and delineated the sequence of genomic events during breast cancer progression. On this trajectory of genomic progression, we identified a subpopulation of patients with very early HER2 amplification. Because early changes have the highest probability of being shared by genetically unstable tumor cells, the genetic characterization of disseminated tumor cells provides a novel rationale for selecting patients for targeted therapies.
authors.affiliation: Institut für Immunologie, Ludwig-Maximilians Universität München, Germany.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Schardt
authors.forename: Manfred
authors.initials: M
authors.lastname: Meyer
authors.forename: Claudia H
authors.initials: CH
authors.lastname: Hartmann
authors.forename: Falk
authors.initials: F
authors.lastname: Schubert
authors.forename: Oleg
authors.initials: O
authors.lastname: Schmidt-Kittler
authors.forename: Christine
authors.initials: C
authors.lastname: Fuhrmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Polzer
authors.forename: Marco
authors.initials: M
authors.lastname: Petronio
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Klein
mesh_terms: D017209:Apoptosis; D001854:Bone Marrow Cells / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D043171:Chromosomal Instability / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D007633:Keratins / Q000235:genetics*; D019656:Loss of Heterozygosity
chemical_list: D005819:Genetic Markers; D007633:Keratins