In patients with Fanconi anemia (FA) one of the DNA repair mechanisms that normally protects us against cancer no longer works adequately. Dutch researcher Najim Ameziane set out to find the genes responsible for this defect.
He discovered a new FA gene and established that FA gene defects could also cause cancer in people who do not suffer from FA. Although this does not sound positive, it is in fact good news. That is because cells with a FA defect are hypersensitive to certain types of chemotherapy and can therefore be specifically targeted.
DNA is continuously damaged. This is normally not a problem because our proteins repair the damaged DNA. However, in patients with FA that is a different story. They have a congenital defect as a result of which the DNA is not repaired. Therefore errors accumulate. These errors can result in uncontrolled cell division. Many patients are therefore confronted with cancer at an early age.
Thirteen different genes, including the well-known breast cancer gene BRCA2, can cause FA if any one of these is defective. These thirteen genes code for proteins that function in a biochemical pathway, the so-called Fanconi anemia (FA) pathway, to repair the DNA. FA patients have a defect in one of these 13 proteins, as a result of which the pathway no longer functions and they run a high risk of developing cancer. However, now the question is whether errors in this pathway can also cause cancer in patients without FA.
Targeted treatment
To determine whether errors in the FA pathway in people without FA can cause cancer, all of the genes involved in that pathway need to be identified. Before Ameziane started his PhD research, only eight of the genes in the pathway had been identified. Now thirteen genes are known and there are strong indications that even more genes are involved. During his analysis of genetic material from FA patients, the researcher discovered one of the new genes that constitute part of the FA pathway. This gene, just like BRCA2, appears to be responsible for an increased risk of breast cancer.