| Title |
Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients
|
|---|---|
| Published in |
Molecular Oncology, December 2014
|
| DOI | 10.1016/j.molonc.2014.12.001 |
| Pubmed ID | |
| Authors |
Marta Pestrin, Francesca Salvianti, Francesca Galardi, Francesca De Luca, Natalie Turner, Luca Malorni, Mario Pazzagli, Angelo Di Leo, Pamela Pinzani |
| Abstract |
Circulating Tumor Cells (CTCs) represent a "liquid biopsy of the tumor" which might allow real-time monitoring of cancer biology and therapies in individual patients. CTCs are extremely rare in the blood stream and their analysis is technically challenging. The CellSearch(®) system provides the enumeration of CTCs with prognostic significance in patients with metastatic breast cancer (mBC), but it does not allow their molecular characterization, which might be useful to identify therapeutically relevant targets for individualized treatment. Combining the CellSearch(®) and DEPArray™ technologies allows the recovery of single CTCs as a pure sample for molecular analysis. The purpose of the study was to investigate the heterogeneity of PIK3CA mutational status within single CTCs isolated from individual mBC patients. CTCs were enriched and enumerated by CellSearch(®) in blood samples collected from 39 mBC patients. In 20 out of 39 patients enriched samples with ≥5 CTCs were sorted using DEParray™ to isolate single CTCs or pools of CTCs to be submitted to Whole Genome Amplification (WGA) before sequencing analysis. In 18 out of 20 patients, it was possible to perform PIK3CA sequencing on exons 9 and 20. Twelve subjects were wild type (wt) for the PIK3CA gene. PIK3CA status could also be assessed in pools of CTCs in seven of these patients, with consistent wt status found. Six patients (33%) had a PIK3CA mutation identified. In 2 of the six patients, molecular heterogeneity was detected when mutational analysis was performed on more than one single CTC, including one patient with loss of heterozygosity on both single and pooled CTCs, and one patient with three different PIK3CA variants on single CTCs but PIK3CA wt status on pooled CTC samples. In six out of the 18 cases PIK3CA status was also evaluable on a primary tumor sample. In one of the six cases a discordance in PIK3CA status between the primary (wild-type) and the matched CTC (exon 20 mutation) was observed. This study demonstrates the feasibility of a non-invasive approach based on the liquid biopsy in mBC patients. Moreover, our data suggest the importance of characterizing CTCs at the single cell level in order to investigate the molecular heterogeneity within cells from the same patient. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 147 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | <1% |
| Netherlands | 1 | <1% |
| Ireland | 1 | <1% |
| Israel | 1 | <1% |
| Mexico | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 141 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 37 | 25% |
| Researcher | 19 | 13% |
| Student > Master | 15 | 10% |
| Student > Bachelor | 10 | 7% |
| Other | 8 | 5% |
| Other | 21 | 14% |
| Unknown | 37 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 29 | 20% |
| Biochemistry, Genetics and Molecular Biology | 28 | 19% |
| Agricultural and Biological Sciences | 21 | 14% |
| Engineering | 7 | 5% |
| Chemistry | 4 | 3% |
| Other | 18 | 12% |
| Unknown | 40 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 March 2015.
All research outputs
#13,723,305
of 24,477,448 outputs
Outputs from Molecular Oncology
#810
of 1,635 outputs
Outputs of similar age
#175,897
of 370,905 outputs
Outputs of similar age from Molecular Oncology
#11
of 24 outputs
Altmetric has tracked 24,477,448 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.