230P - Feasibility of genetic aberrations analysis in the circulating tumor cells (CTCs)

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Translational Research
Presenter Jenny Antonello
Authors J. Antonello1, E. Rossi2, U. Basso3, A. Facchinetti2, V. Zagonel4, J.F. Swennenhuis5, L.W. Terstappen5, A. Amadori1, R. Zamarchi1
  • 1Immunology And Molecular Oncology, IOV-IRCCS, 35128 - Padova/IT
  • 2Department Of Surgery, Oncology And Gastroenterology, University of Padova, 35138 - Padova/IT
  • 3Medical Oncology, IOV-IRCCS, 35138 - Padova/IT
  • 4Department Of Oncology, IOV-IRCCS, 35138 - Padova/IT
  • 5Medical Cell Biophysics, University of Twente, Twente/NL

Abstract

Background

In current practice cancer tissue is taken at diagnosis to assess the presence of treatment targets. This however is suboptimal since tumor cells evolve due to genomic instability. Assessment of the genotype and phenotype of the CTCs will provide insights into which treatments would be most beneficial for the individual patient. Feasibility to detect treatment targets in CTCs has been demonstrated (Meng, Tripathy et al. 2004; de Bono, Attard et al. 2007; Rossi, Basso et al. 2010; Wang, Pfister et al. 2010). In this context, the development of a cytogenetic assay for CTCs will be crucial for successful molecular targeted therapy in cancer patients. Genetic characterization of CTCs is expected to gather new knowledge on the mechanism of metastasis and on potential targets of novel therapeutic strategies.

Patients and methods

Assay optimization for analysis of genetic aberrations of CTCs was performed with cells from tumor cell lines. Tumor cell lines with known chromosomal aberrations and mosaicism were spiked into 7.5mL whole blood samples, at numbers similar to those observed in-vivo in cancer patients. Tumor cells were enriched by CellSearch System and off-line purified and individually analyzed for chromosomal alterations. The procedure was next validated by using blood samples collected from cancer patients.

Results/Conclusions

A robust protocol for the isolation of individual CTCs followed by DNA extraction and amplification after CellSearch enrichment was established. The number and the quality of CTCs needed to obtain an informative analysis of chromosomal aberrations were set up. Accrual of cancer patients for individual CTC isolation and molecular characterization is ongoing. Updated data including evaluations on prognostic value of the genetic aberrations analysis of the CTCs and correlation with clinical stage, tumor burden, metastatic sites and survival will be available and presented at the meeting.

Disclosure

All authors have declared no conflicts of interest.