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Content archived on 2024-05-29

Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies

Final Report Summary - DISMAL (Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies)

The main objective of the DISMAL project was to improve the specificity and sensitivity of current platforms for circulating (CTC) and disseminated tumour cell (DTC) detection in patients with epithelial tumours, as they are the most common types of solid tumours in the EU (approximately 2.5 million new cases each year).

Major achievements included the establishment of a DTC-related multi-centre biobank. This biobank was required to enable the profiling studies performed as an initial step to identify potential DTC-related genes and pathways. To follow enrolment of samples, experimental results and patient data, a common database was developed (please see online). The iCHIP database not only allows archiving of clinical data, but also allows storage of large microarray or proteomics datasets linked to the samples. After DTC / CTC status had been determined the samples were uploaded in iCHIP, and the biobank was continuously updated and contains now samples from 537 breast cancer, 382 colorectal cancer, 158 head and neck cancer and 39 lung cancer patients as well as 56 brain metastases. Besides the clinical information, in total now 848 hybridisations have been uploaded into iCHIP, data of 358 expression arrays and 490 CGH arrays. This is a unique series of valuable data that can be mined in the future. The coordinator will manage requests of DISMAL partners for information the coming years to allow DISMAL members to publish their results. Patent applications will be considered. The project also succeeded in in developing a mouse mammary carcinoma stem cell line (GeTo cells) as a model for DTCs that have the property of outgrowth. GeTo cells mimic the phenotypic heterogeneity with regard to expression of different marker proteins in vitro cultures and form tumours in immune-competent syngeneic mice after orthotopic transplantation in the mammary fat pad with a dose as low as 10 cells, confirming their stemness.

During the complete DISMAL project a large number of results have been generated within the consortium. In total, 41 manuscripts have been accepted for publication in scientific journals, various presentations and posters have been presented. In addition, the International Symposium on Minimal Residual Cancer about disseminated malignancies was organised on 19-22 September 2007 (please see online). All scientific partners of the consortium have contributed to this conference with oral and poster presentations. To disseminate project information to other scientists and to the public, the DISMAL website (please see online) is providing an update on project-related results. In a protected part of the website latest project information is made available to the consortium and will become public after publication of the research results.