Cancer development in older adults

A NEW study by researchers at Dana-Farber Cancer Institute offers fresh evidence for a theory of why incidences of certain cancers grow more common as people age.

The theory is that in tissues that undergo continual renewal, a process where cells die and are replaced throughout life, such as those in the breast, skin, prostate, and colon - a genetic mutation causes some cells to keep dividing even after their chromosomes have lost their protective protein ends called telomeres. The result is chromosomes that fuse together in abnormal ways, creating chaos with cells' genetic programming and setting them on the path toward cancer.

The new study, led by Dr. Ronald DePinho and colleagues and published in Nature, involved the development of a new strain of mice whose ability to develop certain cancers resembles that of humans.

Normally, mice with flaws in their genetic "brakes" against cancer develop lymphomas and malignancies known as sarcomas in bones and connective tissue. In aging humans, however, tumours tend to arise in "epithelial" cells - cells that regularly die and are replaced - that line the interior of certain organs.

The DePinho team speculated that the reason for this difference lay in the telomeres. In humans, telomeres shorten each time a cell divides until they become so short they can no longer protect the chromosomes from damage. At this point, known as the "Hayflick limit," the cells normally cease dividing. In some cells, however, a genetic error enables them to bypass the Hayflick limit and continue dividing even though their chromosomes are virtually shorn of telomeres. At this stage, known as "crisis," the cells' chromosomes begin breaking and fusing in abnormal places.

"When these complex chromosomal rearrangements occur, you get very rapid gains and losses of genetic information within cells," lead author Artandi says. "This process, known as "crisis," gives rise to pre- cancerous cells that begin to form a primary tumor, but cannot fully develop until telomere function is restored." At this point, full maturation of the cancer is achieved by reactivation of the enzyme telomerase, rebuilding and stabilising the cells' telomeres - and allowing continued tumor cell division and migration within the body.

"We have long known that cancer is associated with age," senior author, DePinho remarks. "We know it tends to occur in epithelial cells in older adults, and we know the chromosomal structure of these cancer cells is very complex: under a microscope, it looks as though someone threw a grenade into the nucleus where the chromosomes are located. We wanted to find an explanation for these phenomena."

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Section  : Science & Tech
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