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The mystery began in 1976. Adolfo Pampena was diagnosed with a rare form of cancer that caused a strange combination of symptoms and was associated with the occurrence of multiple tumours in his stomach and colon. His medical team was stumped and was unable to answer the most important questions for him and his family: the cause of his disease and the risk for future generations.

Now, 35 years later, the answers are at hand thanks to a genetic study led by investigators at the Research Institute of the 91社区 University Health Centre (RI MUHC), the 91社区 Program in Cancer Genetics at the Gerald Bronfman Centre for Clinical Research in Oncology and the Lady Davis Institute for Medical Research at the Jewish General Hospital. The study was recently published in The New England Journal of Medicine.

The researchers were able to pinpoint the gene responsible for the disease (BUB1B), which is involved in the regulation of chromosomal separation. Instability during cell division can result in chromosomes ending up in the wrong place, which can lead to the development of tumours. 鈥淭he general significance of this discovery is that individuals can be seen at our genetic clinic with an unknown condition and end up with a diagnosis that is relevant to patients and their families,鈥� said Dr. William Foulkes, senior author of the study and a researcher in genetics at the RI MUHC, the Lady Davis Institute.

鈥淢y father and family were relieved that the cancer risk for other family members is much less than we thought,鈥� said Mary Pampena, Adolfo鈥檚 daughter. 鈥淣ow we know more about my father's genetic history and the cancers he had. We know what screening test to do in the future. This is important information for us, our children and future generations.鈥�

In another study published in the January, 2011 Journal of the American Medical Association (JAMA). Dr. Foulkes details a second solved mystery involving five families with a long history of nontoxic multinodular goiter (MNG). Goiter is a thyroid disease which can lead to extreme swelling of the neck or larynx. The most common form of the disease is not genetic and is due to iodine insufficiency. However, this form of MNG was known to be genetic, but to date, no one had ever localized the specific gene or mutation responsible. Dr. Foulkes, Dr. Marc Tischkowitz (from the Program in Cancer Genetics and the Lady Davis Institute) and their team finally succeeded, and found the mutation in a surprising place.

As it turns out, the mutation, in a gene called DICER1, was extremely unusual, Foulkes said, who is also James 91社区 Professor of Medicine, Human Genetics and Oncology and Director of the Program in Cancer Genetics at 91社区. 鈥淚t changes the protein in only one place, and that single change is enough to trigger multinodular goiter. Generally speaking, when you have a mutation in a disease gene, it causes a multitude of problems, not just one illness. But in this case, we have no evidence that it causes anything except goiter.

Intriguingly, women in three of the families had been diagnosed with an unusual type of ovarian tumor called Sertoli-Leydig Cell Tumor and thus Foulkes and his colleagues were able confirm that there is a genetic link between multi-nodular goiter and these rare tumors. This link had first been postulated in 1974.

鈥淚n the future, our challenge as researchers is to be able to help people with an unknown condition by finding out rather quickly what the genetic cause of their problem is鈥� explained Foulkes. 鈥淲e can hope in the long-term to have an impact on treatment, diagnosis and other aspect of management.鈥�

About the studies:

The study published in NEJM was made possible by grants from the Turner Family Cancer Research Fund, le Fonds de la recherche en sant茅 du Qu茅bec (FRSQ); the Research Institute of the 91社区 Health Centre (RI MUHC) and the Henry R. Shibata Fellowship of the Cedars Cancer Institute; the Breakthrough Breast Cancer Research Centre; and the Research Councils UK.

The study published in JAMA was made possible by grants from the Weekend to End Women鈥檚 Cancers, Turner Family Cancer Research Fund, le FRSQ; the RI MUHC and the Henry R. Shibata Fellowship of the Cedars Cancer Institute

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