Beating cancer to the punch

A new laboratory can detect the disease by spotting genetic changes long before serious symptoms emerge. Dick Ahlstrom reports

Most cancers occur when copying errors occur in people's DNA, their genetic blueprint. A new diagnostic laboratory at St James's Hospital in Dublin specialises in spotting these errors as a way to fine-tune treatment.

"We know that cancer is a genetic disease and genetic changes cause cancer," says Prof Mark Lawler of St James's. "This lab will take the genetic profile of a patient with leukaemia or other selected cancers to decide the best therapies to use."

Lawler is the chief molecular geneticist and associate professor of experimental haematology at the hospital. He is also the head of the new cancer molecular diagnostics laboratory, the first of its kind here, set up with funding from the Department of Health and Children.

Micheál Martin, the Minister for Health, yesterday attended the official opening of the lab, which will play to the strengths of the hospital's Institute for Molecular Medicine. The institute carries out basic research into DNA and the molecular causes of disease, and what it learns can find very quick reapplications in clinical settings via the new diagnostic lab, he says.

"It very much is using the information from the research to develop a practical service that will help cancer patients. It combines research with something that is practical."

The process does not involve producing a general profile of the person's DNA, says Lawler. They do not trawl for diseases and so do not threaten a person's right to genetic privacy. Rather, it is a powerful method for people who arrive as possible cancer patients to receive more accurate diagnoses and more individual treatment plans.

A patient might come in with a suspected leukaemia or tumour. "It is an acquired genetic change, not inherited," says Lawler. Each disease arises from a specific genetic alteration that produces a characteristic disease pattern. "We can use the slight changes that have taken place and give an early diagnosis."

These genetic markers are known for about 10 types of leukaemia and four or five lymphomas, he says. The new lab looks for signs of these genetic changes to provide accurate diagnoses of the diseases involved. "That informs us about the therapy that the patient should get."

The method allows a clear diagnosis often before the major symptoms that would confirm a disease begin to arise, he says. Different methods are used, depending on the disease: some use DNA, others use RNA, a genetic code produced from DNA that contains the recipe used by the cell to make a protein.

One form of leukaemia is caused when an error in DNA duplication causes the "ABL" gene normally found on chromosome 9 to jump into a position adjacent to the "BCR" gene on chromosome 22, known as a BCR-ABL rearrangement, explains Lawler. This translocation event leads to increased resistance to cell death, he says: a typical sign of cancerous growth. This diagnosis uses the patient's RNA.

Tests done at the cancer molecular diagnostics laboratory will show if this rearrangement is present. The usual treatment is a bone-marrow transplant, and the availability of these test methods remains very important afterwards, explains Lawler.

Tests will show if any marrow cells affected by the BCR-ABL rearrangement remain, cells that could cause a relapse. "If we can detect a relapse early we can go in and save the patient before they go into clinical relapse."

Another test is used for lymphomas, this time looking at DNA. If a lymph cell becomes cancerous, it and all subsequent daughter cells will have a characteristic "clonal rearrangement". The lab can confirm this diagnosis very early in the course of the disease, before most conventional diagnostic methods can give an accurate evaluation.