Researchers at the BC Cancer Agency have discovered a gene whose existence may explain the ability of cancer tumours to grow and thrive, as described in a paper published in the prestigious journal Cell today.  The research, conducted by an international team led by Dr. Peter Lansdorp at the BC Cancer Agency, brings to light new information about the causes of genetic instability and cell death.

In order for an organism to survive, its cells must be able divide again and again. But each time a cell divides, it loses some of the repeated DNA located at the end of its chromosomes, known as a 'telomeres.' As the telomere becomes shorter, the genetic structure of the cell becomes unstable, leading to genetic rearrangements during cell division and ultimately cell death. The loss of telomere repeats in cells is believed to be part of the normal aging process and tumour cells require maintenance of telomeres in order to survive and keep dividing.

In looking at the causes and controls of telomere loss and cell growth, Lansdorp's paper focuses on the discovery that a particular gene is responsible for regulating the length and stability of telomere repeats. In collaboration with researchers in Toronto and Australia, the Vancouver researchers found that mice born without a particular gene that regulates the length of telomeres died within 10 or 11 days of birth.  The gene, dubbed "Rtel" for "Regulator of Telomere Length," by Lansdorp's team, appears to be essential in preventing genetic instability.

 "While previous studies have provided evidence for several different mechanisms of telomere loss, this one was not known," explains Lansdorp. "In the Cell paper, we describe a novel mechanism of telomere shortening and genetic instability, and a previously unknown helicase - a protein that unwinds DNA at replication forks  - which is essential to prevent this from happening."

Lansdorp proposes that the Rtel gene is needed to unravel knots – known as g-quartets – formed in DNA which make it difficult for cells to replicate DNA properly. "These type  of structures readily form in the laboratory and our data support that these structures are formed in normal cells as well.  If not properly processed, these structures prevent normal base-pairing and DNA replication."

It follows that if loss of telomere length can harm healthy cells, it should also be able to affect the ability of cancer cells to thrive. Within one to two years, Lansdorp hopes to determine if the levels of Rtel are abnormal in human cancer tissue. Early research indicates that Rtel appears to be highly expressed in lymphomas and in brain tumors known as astrocytomas, possibly preserving the ability of such tumor cells to divide. If this is the case, inhibition of Rtel in cancer cells could compromise their ability to grow providing a new target for therapy.

To date this research has largely focused on understanding the role of Rtel in the mouse model, whose corresponding gene in humans is very similar. Lansdorp's team is eager to explore the possibility that over-expression of Rtel may contribute to human cell growth and tumour progression.

The BC Cancer Agency, a part of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer.  It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care.  The BC Cancer Research Centre conducts research into the causes and cures for cancer.

For more information, please contact:

Nicole Adams

Public Relations Officer

BC Cancer Agency

(604) 877.6272

nadams@bccancer.bc.ca