Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis
Circulating tumor cells’ (CTCs) heterogeneity contributes to counteract their introduction in clinical practice. Through single-cell sequencing we aim at exploring CTC heterogeneity in metastatic breast cancer (MBC) patients. Single CTCs were isolated using DEPArray NxT. After whole genome amplifica...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/3925 |
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| author | Tania Rossi Davide Angeli Michela Tebaldi Pietro Fici Elisabetta Rossi Andrea Rocca Michela Palleschi Roberta Maltoni Giovanni Martinelli Francesco Fabbri Giulia Gallerani |
| author_facet | Tania Rossi Davide Angeli Michela Tebaldi Pietro Fici Elisabetta Rossi Andrea Rocca Michela Palleschi Roberta Maltoni Giovanni Martinelli Francesco Fabbri Giulia Gallerani |
| author_sort | Tania Rossi |
| collection | DOAJ |
| description | Circulating tumor cells’ (CTCs) heterogeneity contributes to counteract their introduction in clinical practice. Through single-cell sequencing we aim at exploring CTC heterogeneity in metastatic breast cancer (MBC) patients. Single CTCs were isolated using DEPArray NxT. After whole genome amplification, libraries were prepared for copy number aberration (CNA) and single nucleotide variant (SNV) analysis and sequenced using Ion GeneStudio S5 and Illumina MiSeq, respectively. CTCs demonstrate distinctive mutational signatures but retain molecular traces of their common origin. CNA profiling identifies frequent aberrations involving critical genes in pathogenesis: gains of 1q (<i>CCND1</i>) and 11q (<i>WNT3A</i>), loss of 22q (<i>CHEK2</i>). The longitudinal single-CTC analysis allows tracking of clonal selection and the emergence of resistance-associated aberrations, such as gain of a region in 12q (<i>CDK4</i>). A group composed of CTCs from different patients sharing common traits emerges. Further analyses identify losses of 15q and enrichment of terms associated with pseudopodium formation as frequent and exclusive events. CTCs from MBC patients are heterogeneous, especially concerning their mutational status. The single-cell analysis allows the identification of aberrations associated with resistance, and is a candidate tool to better address treatment strategy. The translational significance of the group populated by similar CTCs should be elucidated. |
| first_indexed | 2024-03-09T04:38:05Z |
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| id | doaj.art-6b267d453eb0428997c3b1fb92b67a08 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:38:05Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6b267d453eb0428997c3b1fb92b67a082023-12-03T13:24:57ZengMDPI AGCancers2072-66942022-08-011416392510.3390/cancers14163925Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell AnalysisTania Rossi0Davide Angeli1Michela Tebaldi2Pietro Fici3Elisabetta Rossi4Andrea Rocca5Michela Palleschi6Roberta Maltoni7Giovanni Martinelli8Francesco Fabbri9Giulia Gallerani10Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyUnit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyUnit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35124 Padova, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyHealthcare Administration, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyCirculating tumor cells’ (CTCs) heterogeneity contributes to counteract their introduction in clinical practice. Through single-cell sequencing we aim at exploring CTC heterogeneity in metastatic breast cancer (MBC) patients. Single CTCs were isolated using DEPArray NxT. After whole genome amplification, libraries were prepared for copy number aberration (CNA) and single nucleotide variant (SNV) analysis and sequenced using Ion GeneStudio S5 and Illumina MiSeq, respectively. CTCs demonstrate distinctive mutational signatures but retain molecular traces of their common origin. CNA profiling identifies frequent aberrations involving critical genes in pathogenesis: gains of 1q (<i>CCND1</i>) and 11q (<i>WNT3A</i>), loss of 22q (<i>CHEK2</i>). The longitudinal single-CTC analysis allows tracking of clonal selection and the emergence of resistance-associated aberrations, such as gain of a region in 12q (<i>CDK4</i>). A group composed of CTCs from different patients sharing common traits emerges. Further analyses identify losses of 15q and enrichment of terms associated with pseudopodium formation as frequent and exclusive events. CTCs from MBC patients are heterogeneous, especially concerning their mutational status. The single-cell analysis allows the identification of aberrations associated with resistance, and is a candidate tool to better address treatment strategy. The translational significance of the group populated by similar CTCs should be elucidated.https://www.mdpi.com/2072-6694/14/16/3925metastatic breast cancercirculating tumor cellscopy number aberrationssingle nucleotide variantssingle cell sequencingnext generation sequencing |
| spellingShingle | Tania Rossi Davide Angeli Michela Tebaldi Pietro Fici Elisabetta Rossi Andrea Rocca Michela Palleschi Roberta Maltoni Giovanni Martinelli Francesco Fabbri Giulia Gallerani Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis Cancers metastatic breast cancer circulating tumor cells copy number aberrations single nucleotide variants single cell sequencing next generation sequencing |
| title | Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis |
| title_full | Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis |
| title_fullStr | Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis |
| title_full_unstemmed | Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis |
| title_short | Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis |
| title_sort | dissecting molecular heterogeneity of circulating tumor cells ctcs from metastatic breast cancer patients through copy number aberration cna and single nucleotide variant snv single cell analysis |
| topic | metastatic breast cancer circulating tumor cells copy number aberrations single nucleotide variants single cell sequencing next generation sequencing |
| url | https://www.mdpi.com/2072-6694/14/16/3925 |
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