On supporting science journalism
If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.
Mutations in the p53 tumor suppressor gene stand behind many aggressive, deadly cancers¿and in fact, half of all cancers. But not melanomas, a class of malignancies renowned for their lack of response to chemotherapy. Scientists from Cold Spring Harbor Laboratory and Memorial Sloan-Kettering Cancer Center report in today's issue of Nature, however, that mutations in another gene encoding a protein called apoptosis activation factor-1 (Apaf-1) characterize these growths. Like p53, Apaf-1 lies in the cellular pathway leading to apoptosis, or programmed cell death. Disruptions anywhere along this pathway can keep it from its usual task, which is causing precancerous cells to self-destruct.
Of significance, the researchers led by Maria Soengas demonstrated that restoring Apaf-1 to melanoma cells made them capable of killing themselves in response to the chemotherapy drug adriamycin. "The loss of Apaf-1 in malignant melanoma is a prime explanation for both the extreme chemoresistance and apparent lack of p53 defects in such cancers," says collaborator Scott Lowe. This finding not only suggests new treatment approaches but also provides options for more accurate diagnosis. In most of the melanomas they studied, one copy of the Apaf-1 gene was deleted. Complete loss of Apaf-1 function arose from so-called transcriptional silencing, which is emerging as a principle mechanism by which tumor suppressor genes in general become inactivated.
