Non-Oncology Applications: 14 of 14

Vascular Malformations

A vascular malformation is a group of blood or lymph vessels that formed incorrectly. These malformations are present from birth and grow as the person grows. Depending on their location, they can cause pain, swelling, disfigurement, bleeding, or pressure on nearby tissue. They are not cancer and do not spread to distant parts of the body.

The underlying cause can still involve a genetic mistake. Early in development, a change can occur in a single cell in one of the instructions that controls how blood vessels grow. The cells descended from that cell carry the change and form the malformation, while the rest of the body does not. A genetic change that is present in only some of a person's cells is called mosaic. That is why an ordinary genetic blood test may miss it: the blood cells being tested may not carry the change at all.

Knowing the exact change can affect treatment. Some of the same cell-growth pathways involved in vascular malformations are also targeted by drugs developed for cancer. Certain drugs can shrink these malformations, and the best choice can depend on which genetic fault is present.

The usual way to identify that fault is to take tissue from the malformation. That is not always easy or safe because the structure being sampled is made of abnormal blood vessels, and some are located where cutting into them would be risky.

Researchers can sometimes look for the change in loose DNA instead. Cells in the malformation die and release DNA like other cells, so fragments carrying the genetic fault may reach a fluid sample. In ordinary blood, though, the malformation contributes only a tiny share of the total DNA and the signal can fall below the limit of detection. Fluid taken from inside or immediately around the malformation contains a much higher proportion of relevant DNA and is more likely to reveal the change.

This is the smallest non-oncology category tracked in the index. The conditions are uncommon, but the test can still be very practical because one genetic result may directly affect which drug a person receives.