Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer

Stella D’Oronzo, Domenica Lovero, Raffaele Palmirotta, Luigia Stefania Stucci, Marco Tucci, Claudia Felici, Eliano Cascardi, Carmela Giardina, Paola Cafforio, Franco Silvestris

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number17276
JournalScientific Reports
Issue number1
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

  • General


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