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

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...

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Autores principales: D’Oronzo, Stella, Lovero, Domenica, Palmirotta, Raffaele, Stucci, Luigia Stefania, Tucci, Marco, Felici, Claudia, Cascardi, Eliano, Giardina, Carmela, Cafforio, Paola, Silvestris, Franco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872745/
https://www.ncbi.nlm.nih.gov/pubmed/31754145
http://dx.doi.org/10.1038/s41598-019-53660-x
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author D’Oronzo, Stella
Lovero, Domenica
Palmirotta, Raffaele
Stucci, Luigia Stefania
Tucci, Marco
Felici, Claudia
Cascardi, Eliano
Giardina, Carmela
Cafforio, Paola
Silvestris, Franco
author_facet D’Oronzo, Stella
Lovero, Domenica
Palmirotta, Raffaele
Stucci, Luigia Stefania
Tucci, Marco
Felici, Claudia
Cascardi, Eliano
Giardina, Carmela
Cafforio, Paola
Silvestris, Franco
author_sort D’Oronzo, Stella
collection PubMed
description 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.
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spelling pubmed-68727452019-12-04 Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer D’Oronzo, Stella Lovero, Domenica Palmirotta, Raffaele Stucci, Luigia Stefania Tucci, Marco Felici, Claudia Cascardi, Eliano Giardina, Carmela Cafforio, Paola Silvestris, Franco Sci Rep Article 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. Nature Publishing Group UK 2019-11-21 /pmc/articles/PMC6872745/ /pubmed/31754145 http://dx.doi.org/10.1038/s41598-019-53660-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
D’Oronzo, Stella
Lovero, Domenica
Palmirotta, Raffaele
Stucci, Luigia Stefania
Tucci, Marco
Felici, Claudia
Cascardi, Eliano
Giardina, Carmela
Cafforio, Paola
Silvestris, Franco
Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title_full Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title_fullStr Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title_full_unstemmed Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title_short Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
title_sort dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872745/
https://www.ncbi.nlm.nih.gov/pubmed/31754145
http://dx.doi.org/10.1038/s41598-019-53660-x
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