SickKids researchers discover predictive marker for early onset cancer in some cancer-prone families

    TORONTO, Feb. 15 /CNW/ - Researchers at The Hospital for Sick Children
(SickKids) have found that the rate of shortening of the ends of chromosomes
in the white blood cells in people with Li-Fraumeni syndrome can predict the
time of the onset of tumour development. This research is reported in the
February 15 issue of the journal Cancer Research.
    Li-Fraumeni syndrome is a familial cancer syndrome which predisposes
primarily children and young adults to develop cancer. This disease affects
1 in 10 000 people and those diagnosed carry an almost 50 per cent chance of
developing cancer before the age of 20. Even more dramatically, almost all
women with Li-Fraumeni syndrome will develop cancer in their lifetime, 55 per
cent of them developing breast cancer. A major question has always been when.
    "Several years ago, we and others discovered that people with Li-Fraumeni
syndrome had inherited a mutation of the p53 gene, and this resulted in
dramatic occurrences of cancer. We also noticed that cancers were developing
at younger and younger ages with each successive generation in each family,"
said Dr. David Malkin, the study's principal investigator, staff oncologist
and co-director of the Cancer Genetics Program, senior scientist in Genetics &
Genome Biology at SickKids, professor of Paediatrics at the University of
Toronto. "We wondered why different members of the family develop cancer at
different times, if each affected family member carried the identical specific
mutation in the p53 gene."
    Each time a normal cell divides, its chromosomes, which contain the
cell's genetic material, divide as well and their ends, known as telomeres,
will shorten slightly. After many generations of cell divisions, the
chromosomes eventually shorten to a point where the telomeres do not work
properly and the cell's genetic material becomes unstable.
    "We hypothesize that people with this syndrome are passing on shorter
telomeres and more genomic instability with each generation," said Malkin.
    While this instability means that patients with Li-Fraumeni will get
cancer younger, it also means that clinicians may now have a tool to help
predict at what age these patients will develop cancer. Telomere length may be
used as a prognostic marker to help to predict when it is most appropriate to
begin cancer screening in these patients.
    "This finding means that if a patient has a cancer predisposition
syndrome, you can time the prevention options; when the development of cancer
occurs in this patient becomes less of a mystery," said Dr. Uri Tabori, study
lead author, associate scientist, Genetics and Genomic Biology, staff
oncologist, principal investigator in the Arthur and Sonia Labatt Brain Tumour
Research Centre and assistant professor of Paediatrics at the University of
Toronto. "The most important aspect of this discovery is the concept, and the
impact it will have on the management and treatment of all patients with
cancer predisposition syndromes."
    "While we do not yet know why cancer develops, we now, at least for
patients with this syndrome, have a better idea of when they will develop it."
    Other members of the research team included Sonia Nanda, Harriet Druker
and Jodi Lees, all from SickKids. This research was supported by the National
Cancer Institute of Canada with funds from the Canadian Cancer Society, and
SickKids Foundation.

    The Hospital for Sick Children (SickKids), affiliated with the University
of Toronto, is Canada's most research-intensive hospital and the largest
centre dedicated to improving children's health in the country. As innovators
in child health, SickKids improves the health of children by integrating care,
research and teaching. Our mission is to provide the best in complex and
specialized care by creating scientific and clinical advancements, sharing our
knowledge and expertise and championing the development of an accessible,
comprehensive and sustainable child health system. For more information,
please visit www.sickkids.ca. SickKids is committed to healthier children for
a better world.

For further information: Chelsea Novak, Public Affairs, The Hospital for
Sick Children, (416) 813-5045, chelsea.novak@sickkids.ca