Scientists at the University of Pittsburgh School of Medicine report they have identified a combination of genetic changes—affecting the promoters of TERT and TPP1—that helps explain how many melanoma tumors maintain unusually long telomeres and continue proliferating.
Scientists at the University of Pittsburgh School of Medicine say they have identified a key genetic combination that helps melanoma cells maintain abnormally long telomeres—protective DNA caps at the ends of chromosomes—and continue dividing.
Writing in Science, Jonathan Alder and colleagues reported that promoter mutations affecting TERT, a gene involved in telomerase activity, can work in tandem with mutations in a newly annotated promoter region of TPP1, a telomere-binding protein that can enhance telomerase function. When the team introduced mutated forms of both genes into cells, the combination produced the unusually long telomeres seen in melanoma tumors, according to the University of Pittsburgh’s account of the work.
"We did something that was, in essence, obvious based on previous basic research and connected back to something that is happening in patients," Alder said in the university release.
The report also highlighted the role of Pattra Chun-on—described by the university as an internist pursuing a Ph.D. in Alder’s lab—in investigating why TERT promoter mutations alone were not sufficient to recreate melanoma’s distinctive telomere features in experimental settings.
The university said the research included collaborators from the University of California, Santa Cruz, and Johns Hopkins University, and that it was supported by National Institutes of Health grants R35CA209974 and R01HL135062. Researchers said the findings could point to future therapeutic strategies aimed at disrupting melanoma’s cancer-specific telomere maintenance mechanisms.
