My friend asked me why tumors expression telomerase but with a shorter telomere. Any answer? Also I thought since telomerase activation is so common in all cancers, why telomerase had not been used as a biomarker for cancer?
I've wondered the same thing. Telomerase is also activated in some benign proliferative conditions., so it would not be specific enough for a diagnosis of malignancy. However, I think it may be helpful for our understanding of cancer to know which comes first. Does telomerase activation allow shorter telomeres, or do short telomeres contribute to telomerase activation?
Its likely that telomere shortening occurs first, before a tumour gains the ability to express telomerase and maintain its telomere length. In neuroblastoma for example, there is a subtype that never expresses telomerase, thereby shortening its telomeres during a rapid tumour proliferation phase that eventually results in telomere crisis and spontaneous regression of the tumour. I've also seen studies where pre-cancerous lesions like polyps have shorter telomeres than normal colon tissue, suggesting the telomeres shorten during a proliferative phase when there is no cancer yet. If telomerase is not activated the tumour undergoes telomere crisis and if telomerase is activated then the limitless replicative potential is achieved and you're one step closer to malignancy. There may be examples of telomerase activation occurring before the telomeres shorten, but most data suggests telomerase activation is a later event.
Telomerase activation is not common to all cancers, but common to only about 80% of cancers. However, the ability to extend telomeres is common to all cancers. Those ~20% of cancers that don't have telomerase activation use a mechanism called alternative lengthening of telomeres (ALT) in order to maintain telomere length. Interestingly the cancers which use the ALT mechanism tend to have telomeres that are longer than 'normal' tissue.
Actually Telomerase research has gone far away for diagnosis thing and may be also for prognosis prediction, one of the common themes if hTERT detection.The phenomena of short telomeres with expression of telomerase is just because the whole mechanism of expression is a result for that shortening with a direct aim of maintaining that length avoiding cellular collapse without aiming for elongation it may also be done in a non-expressive fasion by acquiring a much rarer telomerase-independent ALT mechanism, thus bypassing crisis and ultimately leading to cell immortalization.
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