The Cancer Genome Project

Munich 30 November 2000 An other extremely interesting project was the Cancer Genome. Here the normal cells are compared with cancer cells. Systematically they search for changes in the genome sequence. Mike Stratton presented the Sanger approach.

Cancer develops from a singe abnormal cell - an adult human is composed of 100 million million (it is not a 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 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, it begins to behave abnormally, 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 discovered.

Finding 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 by which cancer develop 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.

Cancer Genome Project

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 they 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 they 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 requires an independent program of detection:

  • large homozygous deletions (10kb - 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 not to divide.

Requirements for this Project

This project needs 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 helps in the project.

Mike Stratton expects a 5 to 10 years, as most of the research can be done in parallel with other research institutes. The results are free for research or the pharmaceutical industry.

Uwe Harms

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