NTHL1 is involved in DNA repair. It recognizes a specific form of DNA damage. If a mutation occurs in the NTHL1 gene, the NTHL1 protein does not work. Consequently, the damage is not recognized and not repaired. This leads to even more unrepaired mutations, which is a cause of cancer. Due to mutations in the NTHL1 gene, errors in the DNA where a ‘C’ is replaced by a ‘T’, are not corrected. This occurs at specific locations in the DNA, resulting in a recognizable mutation pattern.
The researchers used a new method to determine that NTHL1 mutations also cause breast cancer and other types of cancer. This method is based on the fact that mutations in the NTHL1 gene cause a specific pattern of other mutations. Because this pattern only occurs in tumors of patients with an NTHL1 mutation, but not in other tumors, the researchers were able to link this pattern to the NTHL1 gene. This method can in future be used to detect new genetic causes of cancer. Roland Kuiper, molecular geneticist at the Princess Máxima Center: “More than 30 such mutation patterns are known, which are not only specific to NTHL1. If all the tumors in a patient with multiple types of cancer have the same mutation pattern, this is a strong indication that a genetic aspect is involved. In that case, all these tumors originated in the same way.” Recently, Kuiper received a grant from the Dutch cancer society (KWF) to apply this technique in research into pediatric oncology.