The aim of the project is to apply completely new and unique techniques of genomic research to the analysis of complex biological systems, such as cancer cells. Capability to establish differences between normal and tumor cells will be instrumental for cloning cancer-causing genes and for early diagnosis and prevention of cancer. New type of microarrays recently developed at the Karolinska Institute for the first time open possibilities for large scale study of methylation patterns in normal and cancer cells. As NotI sites are associated with genes, unique information including gene expression and deletion/amplification data will be obtained. This information will be analyzed to answer the following questions: which of the cancer associated genes are cancer specific and which are common for the different tumors; to develop diagnostic, prognostic and predicting tools; will help to understand the risk of the development of a particular type of the tumors and suggest the most optimal way of treatment; to discriminate between hereditary and environmental factors; involvement of methylation and loss of heterozygosity in the cancer development; estimation of the value gene expression versus genomic chips. Databases with results of hybridization with NotI microarrays will be established. The program-integrating database will also be created.
It is important to mention that recent data suggests that significant progress in the early diagnosis cancer can be achieved with methods based on detecting acquired abnormalities of gene-specific methylation. Thus Palmisano et al. (2000) reported that aberrant methylation of the p16 and/or MGMT promoters can be detected in DNA from sputum in 100% of patients with squamous cell lung carcinoma up to 3 years before clinical diagnosis. Such improved detection of people at greatest risk of lung cancer could greatly reduce mortality from this disease. In fact, the prognosis for patients with highly malignant tumors strongly correlates with the stage of the disease at the time of presentation. Therefore, early identification and intervention strategies stemming from these developments are expected to improve the usually poor prognosis of this fatal disease even before efficient medical treatment of the disease will be developed.
Thus it is clear that project will have strong impact not only for fundamental sciences but can produce products/results (e.g. new TSGs, databases, diagnostic and predictive tests, microarrays, etc.) that can be applied immediately in hospitals and clinics. The project also involves creation of a collection of cancer samples from different parts of Russia and Ukraine and the development of a computer programme analysing data from NotI microarrays. Within this project NIS scientists will learn in Sweden how to produce and work with NotI microarrays and finally will create this facility in their home countries.
B15 2TT Birmingham