Scientists know that melanoma has a genetic component – mutations have been found in up to 40% of families with a high rate of melanoma. If you have a first-degree relative with melanoma, you are 2-3 times more likely to develop the disease. And the more relatives you have with melanoma, the risk rate increases drastically.
There are several genes that seem to be a factor in developing melanoma: CDK4, CDK6, BAP1, and BRCA2. However, the gene CDKN2A is estimated to account for 35% to 40% of all family-related melanomas. It produces a protein named p16 and you may see it referred to by that name in scientific journals as well. Based on research, it appears that mutations of this gene plays a significant role in hereditary melanoma. As a result, it is one of the targets of exploration in developing new techniques and therapies to treat melanoma, particularly late-stage melanoma.
The Nobel Prize was recently awarded to two immunotherapy researchers. And a recently released study in the Journal of Medical Genetics shows that this type of immunotherapy is particularly effective for those who have the inherited CDKN2A mutation.
In the study, researchers investigated whether checkpoint inhibitor immunotherapy (CTLA-4 and PD-1 inhibitors) would be effective for this patient group. From publicly available datasets, they compared the results of the inherited CDKN2A mutation with those who didn’t. The findings were pretty exciting. Nearly 2/3 of the CDKN2A patients saw shrinkage of their tumors. And even more noteworthy was that for 1/3 of the patients, their tumor disappeared completely! Compare that to the expected result of only 1/3 of patients would respond to the treatment.
The other intriguing discovery is that CDKN2A melanoma tumors have a larger number of mutations that those without CDKN2A mutation. The researchers theorize that immunotherapy may work well for the CDKN2A group because those tumors are so mutated that the immune system can more readily recognize those cells to be different from healthy cells.
This is a significant development because carriers with CDKN2A mutations that develop melanoma have poor prognosis rates. Study leader Hildur Helgadottir at the Karolinska Instituet in Sweden states, “We saw that the mutation carriers with metastatic melanoma responded surprisingly well to immunotherapy. This is good news, particularly for this otherwise vulnerable patient group.”