title: High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer.
abstract: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) identifies breast cancer patients with less favorable outcome. Furthermore, molecular characterization is required to investigate the malignant potential of these cells. This study presents a single-cell array comparative genomic hybridization (SCaCGH) method providing molecular analysis of immunomorphologically detected DTCs. The resolution limit of the method was estimated using the cancer cell line SK-BR-3 on 44 and 244k arrays. The technique was further tested on 28 circulating tumor cells and four hematopoietic cells (HCs) from peripheral blood (n = 8 patients). The SCaCGH method was finally applied to 24 DTCs, three immunopositive cells morphologically classified as probable HCs from breast cancer patients and five HC controls from BM (n = 7 patients plus n = 1 healthy donor). The frequency of copy number changes of the DTCs revealed similarities with primary breast tumor samples. Three of the patients had available profiles for DTCs and the corresponding tumor tissue from primary surgery. More than two-third of the analyzed DTCs disclosed equivalent changes, both to each other and to the corresponding primary disease, whereas the rest of the cells showed balanced profiles. The probable HCs revealed either balanced profiles (n = 2) or changes comparable to the tumor tissue and DTCs (n = 1), indicating morphological overlap between HCs and DTCs. Similar aberration patterns were visible in DTCs collected at diagnosis and at 3 years relapse-free follow-up. SCaCGH may be a powerful tool for the molecular characterization of DTCs.
authors.affiliation: Department of Genetics, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Randi R
authors.initials: RR
authors.lastname: Mathiesen
authors.forename: Renathe
authors.initials: R
authors.lastname: Fjelldal
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.forename: Eldri U
authors.initials: EU
authors.lastname: Due
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Geigl
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.forename: Inga H
authors.initials: IH
authors.lastname: Rye
authors.forename: Ida J
authors.initials: IJ
authors.lastname: Schneider
authors.forename: Anna C
authors.initials: AC
authors.lastname: Obenauf
authors.forename: Oliver
authors.initials: O
authors.lastname: Mauermann
authors.forename: Gro
authors.initials: G
authors.lastname: Nilsen
authors.forename: Ole
authors.initials: O
authors.lastname: Christian Lingjaerde
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.forename: Lars O
authors.initials: LO
authors.lastname: Baumbusch
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006801:Humans; D009362:Neoplasm Metastasis