Final Activity Report Summary - LUNG MICROMET (Identification of molecular signatures determining early metastatic spread of lung carcinomas in women)
In this EU- Marie Curie project, the aim was to assess whether the invasiveness and early metastatic spread of primary pulmonary tumours were associated with specific molecular patterns. As a marker for early spread we investigated disseminated tumour cells (DTC) in bone marrow (BM).
Through using a high-resolution comparative genomic hybridisation (CGH) and expression arrays we performed genome wide DNA aberration and expression profiling of primary lung tumours. The genomic aberration profiles of the tumours from patients with and without DTC in the BM were then compared in order to find specific molecular changes associated with DTC status. We could find, for the first time, tumour-specific genetic signatures involved in early hematogeneous dissemination of lung tumours. We also identified five chromosomal regions differentiating BM-negative from BM-positive patients. Copy number changes on chromosome 4q were the most prominent finding, containing the highest number of differentially expressed genes. In BM positive patients 4q was mostly lost, whereas some gains could be found among BM negative patients. Interestingly, loss of 4q was also associated with formation of distant metastases. The same loss was also found to be common in brain metastases from both small and non-small-cell lung cancer patients.
In conclusion, to our knowledge, this is the first study identifying tumour-specific genomic signatures involved in the early hematogeneous dissemination of lung tumour cells. Furthermore, we could show that loss of 4q might also be an important determinant for outgrowth of distant metastases. It will thus be an important goal in future studies to identify the target gene within 4q and explore its functional relevance.