Genomics

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High-resolution analysis of copy number changes in circulating and disseminated tumor cells in breast cancer patients


ABSTRACT: The aim of this study was to establish a single-cell array comparative genomic hybridization (SCaCGH) method providing in-depth genomic analysis of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The robustness and resolution limits of the method were estimated with different cell amounts of the breast cancer cell line SKBR3 using 44k and 244k arrays. Subsequent adjustments of the method were conducted analyzing the copy number profiles of 28 CTCs in combination with four hematopoietic cell (HC) controls from eight metastatic patients and of 24 DTCs, three probable HCs, and five HC controls from seven breast cancer patients and one healthy donor. The frequency of the major genomic gains and losses of the analyzed DTC revealed similarities to primary breast tumor samples with some evident differences. Three of the patients had available profiles for DTC and the corresponding primary tumor. In 2/3 of the examined DTCs, equivalent genomic changes and common aberration breakpoints were disclosed, both to each other and to the corresponding primary tumors. Interestingly, similar copy number changes were found in DTCs taken at time of diagnosis or in DTCs collected at 3-years relapse-free follow up. Residual immunomorphological characterized tumor cells showed balanced profiles with only minor aberrations. Three cells with unclear morphological identification showed either balanced profiles (n=2) or aberrations comparable to the primary tumor and DTC (n=1). SCaCGH may be a powerful tool for molecular characterisation of immunostained and morphological identified CTCs and DTCs to explore the malignant potential, therapeutic targets and tumor heterogeneity of single tumor cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27574 | GEO | 2012/11/19

SECONDARY ACCESSION(S): PRJNA181273

REPOSITORIES: GEO

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