Genetic factors influencing telomere length affect the risk of specific glioma subtypes

genetic risk factors for glioma subtypes

Telomeres are DNA-based "caps" that exist on the ends of chromosomes. These "caps" are composed of a hexanucleotide unit "TTAGGG" which is repeated tens to thousands of times at the end of the chromosome, and help stabilize the end by attracting specific proteins. When cells are young, telomeres are long; this is also true of telomeres in germ cells and embryonic cells. As cells age, telomeres progressively shorten until they degrade completely; this degradation process signals the end of the life for a particular cell as it then becomes genetically unstable and dies. 

Glioma geneticists have recently found that at least four different genetic polymorphisms in genes that control telomere function are also associated with glioma case status. Interestingly, some of these same genetic factors were "top hits" for telomere length in prior genome-wide association studies. This means that the control of telomere length likely affects the risk of glioma. One might surmise that shortened telomeres may increase risk of cancer, since degraded telomeres can lead to genetic instability and mutation. However, the reverse is true -- glioma risk increases with longer telomeres.

The figure here shows the identity of specific genetic factors that influence telomere length and brain cancer risk. Inherited variation in the genes TERT, RTEL1, POT1, and TERC are shown in green at the left side of the figure. These factors can influence all glioma risk (TERT and RTEL1), or just some subtypes (POT1 and TERC). Mutations can also occur in some genes during the carcinogenic process; these mutations are acquired only in the tumor cells and are not inherited. Such mutations can occur in ATRX and TERT as indicated. Other hallmark mutations are indicated in the figure, including TP53, 1p19qDel, RB1 and p16.  

To get more information, please read:this abstract; or the complete paper.

An additional recent publication can be located here.