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Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Enumeration of circulating tumor cells (CTCs) may reflect the metastatic potential of breast cancer (BC). By using the DEPArray, we investigated CTCs with respect to their epithelial-to-mesenchymal transition phenotype and compared their genomic heterogeneity with tissue biopsies. Seventeen stage IV BC patients were enrolled. Pre-enriched CTC suspensions were stained with fluorescent-labeled antibodies to epithelial (E) and mesenchymal (M) markers. CTC samples were processed by DEPArray system and clustered in relation to their markers. DNA from CTCs, as well as from primary tumor samples, was sequenced by next generation sequencing to assess the mutational state of 50 major cancer-related genes. We identified four different CTC subsets that harbored different gene variants. The most heterogenous CTC subsets included the M+/E− phenotype, which, however, expressed only 7 repeatedly mutated genes, while in the M−/E+ subset multiple mutations affected only 2 out of 50 genes. When matching all gene variants among CTC subsets, a small number of mutations was shared by only 4 genes, namely ATM, FGFR3, PIK3CA, and TP53 that, however, were absent in primary tumors. Our results postulate that the detected mutations in all CTC subsets may be considered as genomic markers of metastatic dissemination to be investigated during early stages of BC.
- Subjects :
- Adult
Epithelial-Mesenchymal Transition
Class I Phosphatidylinositol 3-Kinases
Tumour heterogeneity
DNA Mutational Analysis
lcsh:Medicine
Breast Neoplasms
Ataxia Telangiectasia Mutated Proteins
Biology
Article
DNA sequencing
Breast cancer
Circulating tumor cell
Biomarkers, Tumor
medicine
Humans
Receptor, Fibroblast Growth Factor, Type 3
Breast
lcsh:Science
Gene
Multidisciplinary
Base Sequence
lcsh:R
Genetic Variation
High-Throughput Nucleotide Sequencing
Cancer
Middle Aged
Neoplastic Cells, Circulating
medicine.disease
Primary tumor
Phenotype
Mutation
Cancer research
biology.protein
lcsh:Q
Female
Single-Cell Analysis
Tumor Suppressor Protein p53
Antibody
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....5e8d7e0c97f3b79fe93679c55a87a995