Telomere Maintenance Mutations and Cancer Cell Immortality
New research has identified mutations that could lead to the lengthening of telomeres, a hallmark of cancer cells and an important focus in developing targeted treatments. Published in Nature Communications, scientists from the German Cancer Research Center looked at cancer cells to find the ways some of them achieve immortality in a study as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG).
Telomeres are special sections of DNA found on the end of chromosomes that are essential for maintaining chromosomal and genomic stability. Every time a cell divides, telomeres become shorter until they reach a minimum length and thus have a natural expiry date. Stem cells can produce telomerase, an enzyme that can lengthen telomeres and make them “immortal”, and are the only cell type to do so.
Previous studies have shown that around 85% of cancer cells upregulate the telomerase enzyme through a different mechanism to lengthen telomeres.
More than 2,500 tumour genomes of 36 types of cancer were analysed and the team found DNA mutations pointing to one of the two known mechanisms to lengthen telomeres in 13% of the cases. The researchers reported that in most of the 2,500 cancer cases studied, telomerase gene activity was increased but had no genomic changes to explain it, and possibly could be due to epigenetic factors instead.
In the 13% of cases with DNA mutations for telomere lengthening, only 20% pointed to the alternative mechanism. The telomeres in these cells contained variations of the normal telomere sequences usually found, and other parts of the genome were found to contain small fragments of telomeres where they shouldn’t be.
The aggressiveness of childhood cancers in particular can be determined by the mechanism used to lengthen telomeres, such as medulloblastomas, where the alternative telomere lengthening mechanism is associated with a worse prognosis.
The results are yet to be definitive for determining whether the two findings affect the course of disease in different cancer types. The team will continue to research on these important findings and potentially identify all the underlying molecular processes taking place, as well as developing targeted treatments for patients with cancer.