Sanger's Cancer Genome Project requires another 5 to 10 years of research

Munich 30 November 2000One of the most intensive research programmes at the British Sanger Centre for genomics constitutes the Cancer Genome Project. In this project, the normal cells are compared with cancer cells. Systematically, the scientists are searching for changes in the genome sequence. Mike Stratton presented the Sanger approach in the ongoing fight against cancer.

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Cancer develops from a singe abnormal cell. An adult human being is composed of 100 million million (this is no typing error!) cells. It arises when a single cell begins to behave abnormally. The cell divides when it should be quiescent. It invades and ultimately metastases throughout the body.

Mike Stratton stated that cancer is a disease of DNA. Throughout life, all cells are exposed to chemicals, to radiation and to all sorts of viruses. These agents induce changes in the DNA sequence. When a single cell acquires a sufficient number of changes in DNA sequence in the relevant genes, then it begins to behave abnormally, which is characteristic of a cancer. In a single cancer, many different genes are mutated. Different genes are mutated in different cancers and many cancer genes remain to be unveiled.

Discovering the cancer genes helps to understand the mutated genes, their combinations and how they are mutated. It gives insight in causes of cancer, biological mechanisms through which the cancer develops and appropriate therapeutic targets. Cancer needs 20 to 50 years to develop abnormally. Mike Stratton felt like an archaeologist, looking what happened to the cell 20 years ago.

The availability of the human genome sequence has a major impact on the cancer gene discovery. It changes the types of genes one can look for. Now scientists can search much larger parts of the genome and ultimately the whole genome. It tells how many genes are abnormal in each cancer and how cancers differ from each other. Finally, researchers get a complete picture of the biological forces that are driving cancers.

Mike Stratton listed five classes of structural abnormalities in cancer cells, which each require an independent programme of detection:

  • large homozygous deletions (10 kb - 10 mb)
  • small intragenic mutations - base substitutions and small deletions/insertions
  • rearrangements
  • methylation
  • amplification
The deletions for example mean that there are holes in the DNA. The DNA no longer contains the information as indivisible data.

The Cancer Genome Project has a need for automatic, robotic, factory-type infrastructure for analysis of samples. Additional large machine resources and powerful computing and bioinformatics tools are necessary. Tissues of normal cells and tumours from patients are a big help in the project. Mike Stratton expects another 5 to 10 years of project development, as most of the research can be done in parallel with other research institutes. The results are freely available for the scientific community and for the pharmaceutical industry.


Uwe Harms

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