There were 13 people in attendance. Joyce gave a welcome and overview of what is going on in the VHL Family Alliance. She told us that we are now in touch with nearly 7,000 peoople with VHL in 27 countries! This is a long way from 1993 when many of us first heard about the VHL Family Alliance.

Dr. William Kaelin gave a wonderful, easy to understand presentation of the work going on in his research lab, to identify the function of the VHL protein. He also introduced us to three researchers on his team who have made some of the breakthroughs in the work.

Dr. Kaelin explained to us that everybody carries two copies of the VHL gene. The VHL gene is a tumor suppressor gene, and only one copy of the VHL gene needs to remain intact for the cells to function normally. One copy of the VHL gene is inherited from each parent. Since the copy inherited from the parent without VHL is healthy and usually functioning, most cells are fine. But if that second copy of the VHL gene gets changed by some environmental impact, then a tumor begins to form.

This same series of events can occur sporadically, in a person who inherited two working copies of the VHL gene. In this case, both copies of the VHL gene in a single cell have to be changed so that they do not work properly.

Kaelin’s team has shown in the lab that if VHL tumor cells in a mouse is injected with the normal VHL genetic material, the cell normalized and the tumor shrinks. This shows that there is hope for therapies based on replacing the genetic material, or replacing the VHL protein in tumor cells.

Kaelin also went on to describe what they believe to be the role of the VHL protein in signalling a loss of oxygen in the cell. Erythrocythemia (too many red blood cells) is sometimes seen in people with VHL. Normally, this would be the body’s response to too little oxygen — if you were on a high mountaintop or in a cave with limited oxygen, the body would make extra red blood cells to pull as much oxygen out of the air as possible. This was one clue which led them to see that the absence of the VHL protein tells the cell that there is not enough oxygen, so the cell sends out distress signals that it needs more oxygen. In the case of a wound, where additional oxygen is needed for repair, the body’s normal response is to build more blood vessels to bring more blood to bring more oxygen. In VHL, however, these additional blood vessels create a hemangioblastoma.

The process is ongoing to identify the functions of the VHL protein, so that scientists can understand how they might intervene in the chain of events and change the outcome. He explained one method for finding other types of proteins with similar traits. If they can restore the function of the VHL gene, or substitute another drug for the VHL protein, or change the reaction of the chemical that calls for blood vessel construction, then they may be able to stop the development of a tumor.

Research on the kinds of mutations (genotypes) that occur in the VHL gene may lead to a better understanding of the particular manifestations of VHL that people in that genotype may encounter.

Dr. Kaelin’s talk was very interesting and informative, and we are all invited to tour Dr. Kaelin’s lab in the Dana Farber Cancer Research Institute in Boston.

We also announced that the VHL Family Alliance is forming a Team VHL to take part in the 1997 Boston Marathon Jimmy Fund Walk, Dana Farber’s annual fund-raiser. This walk will take place on Sunday, September 28, 1997, and we will have more information at a later date. We need both walkers and sponsors. All money raised goes to Dana Farber Cancer Research Institute, where it will be directed to Dr. Kaelin’s team to work on the VHL protein. For more information, contact Laurel at, 617-324-1821.

As published in the VHL Family Forum, newsletter of the VHL Family Alliance, June 1997