A collaborative research effort by scientists at the Duke Cancer Institute, Johns Hopkins, and several other participants have identified gene mutations in TERT promoters. These abnormalities can trigger malignant cells and encourage them to perpetually proliferate. Immortal cell replications are found in several cancers of the liver, skin (melanoma), urinary tract, and brain.
Understanding cellular mechanisms responsible for immortal cells and early detection of cancerous biomarkers may greatly improve diagnosis and prognosis for patients afflicted with brain tumors and other cancers.
The study, published in the journal Proceedings of the National Academy of Sciences, analyzed how some malignant cells are able to proliferate uncontrollably while normal cells will replicate to a certain point and then undergo apoptosis (death). Over 70 billion cells in the average human adult die each day due to the natural phenomenon of programmed cell death.
As scientists have found in priors years of study, telomeres are a vital component in immortal cell replication. A telomere is a region of repetitive nucleotide sequences at each end of a chromatid. A chromatid contains the replicated DNA of each individual chromosome which is joined by a centromere for the process of cell division (mitosis or meiosis).
The purpose of a telomere is to protect the end of the chromosome from deterioration and prevent fusion with neighboring chromosomes while the cell is dividing and replicating. Telomeres are consumed during cellular division. They are then replenished by an enzyme called telomerase which serves as a temporary growth factor.
Telomerase expression plays a role in cellular senescence (biological aging). The telomeres endure a shortening mechanism which normally limits cells to a fixed number of divisions (Hayflick limit), which is essentially aging on a cellular level. Once the cell has peaked division limits, it will no longer replicate and will expire.
Telomerase reverse transcriptase (TERT), a catalytic subunit of telomerase, temporarily maintains the length of the telomeres which enables the cell to continue proliferating.
Abnormalities or genomic instability in DNA replication can lead to immortal cells. Cancer is the uncontrolled growth of abnormal cells in the body. Most cancers are the result of immortal cells which evade cellular expiration.
The process of telomere shorting does not take place in cancer cells due to the telomerase enzyme not being repressed. Instead, the enzyme maintains telomere length, never shortening.
A TERT promoter gene, which controls the directives for making the telomerase enzyme, is involved in some cancer tumors. A mutation of the TERT promoter gene essentially creates a constant growth spurt promoting the telomeres to never shorten. Thus cancer cells are effectually programmed with an infinite replicative potential.
One of the most fascinating and oldest examples of immortal cell lines used in scientific research are HeLa cells, cultured cervical cancer cells from a woman referred to as Henrietta Lacks. The cells were initially harvested back in 1951.
The current research expanded on how mutations in a TERT promoter gene contributed to cell immortality in melanomas, inspiriting further analysis of more than 1,200 tumors across 60 different types of cancer.
This analysis revealed nine tumor types from cancers like melanomas and medulloblastomas which were linked with TERT promoter abnormalities and shared commonalities suggesting they required a mutation in order to trigger irregular telomerase production.
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