A study finding that a combination of genetic variants underlie melanoma's ability sustain telomere maintenance and drive its growth is reported in Science this week. The finding, described by team led by University of Pittsburgh scientists, may help in the development of new treatments for cancer and other diseases. Overcoming replicative senescence is an essential step during oncogenesis, and telomere lengthening has been shown to be one way tumor cells increase their replicative capacity. TERT is a key to telomere synthesis and maintenance, and while promoter mutations in the gene are found in 75 percent of melanomas, they are not sufficient to maintain telomeres alone. Aiming to uncover new mechanisms of telomere maintenance in cancer cells, the researchers analyzed somatic mutations that occur in telomere-related genes. They find that mutations in a telomere binding protein called TPP1, which are often present in melanoma, synergize with TERT to lengthen telomeres melanoma. "The identification of new pathways that contribute to telomere lengthening and cellular immortalization may have important prognostic value and may also inform the development of possible treatments for patients with cancer and those with diseases of telomere shortening," the study's authors write. "Our findings also support the idea that multiple noncoding mutations can cooperate to enable cellular immortalization and highlight the importance of understanding the contribution of noncoding variants to the development of cancer."
Pitt Team Uncovers Key Mechanism Behind Immortalization in Melanoma
Nov 11, 2022