Bcl-10 Gene Mutated in Many Cancers, UK Study Finds

by Jacqueline Strax

January 8, 1999. British scientists reported today that they have found a new gene mutation, which plays a key role in metastasis of common forms of cancer. They isolated the gene from tumor samples of patients in the UK
      The mutated gene, Bcl-10, was originally investigated only in B cell non-Hodgkin's lymphoma, a rare cancer. But Dr Martin Dyer and his team at the Institute of Cancer Research report that the gene is mutated in many tumor types.
      The discovery could eventually lead to a new drug to treat common types of cancer. The researchers expect their dicovery to greatly increase knowledge of the way cancer spreads.
      Interviewed by BBC Science Correspondent James Wilkinson, Dr. Dyer said that mutated Bcl-10 "may be commonly involved" in many cancers. The research team compares Bcl-10 with p53, which is mutated in almost 50% of cancers.

      The new study indicates that cancer cells with mutated p53 do not also have mutated Bcl-10. So, they suggest, research into both of these genes might cover a broad spectrum of common cancers.
      The gene was isolated from a sample tumor of a man with MALT B-cell lymphoma of the stomach. The Bcl-10 in the tumor, having mutated, was unable to do its normal job of triggering apoptosis (programmed cell death), the process of making damaged cells die off.
      Normal p53 and Bcl-10 molecules, Wilkinson explains, "act as quality control inspectors, preventing cancerous cells from reproducing. Mutant Bcl-10 makes cells cancerous." Mutant Bcl-10 not only prevented abnormal cells from dying and speeded up their reproduction - like p53 - but also, the scientists found, actively changed cells so they become malignant.
      P53 research has advanced to the point of looking at treatments putting normal p53 molecules into cells. The BBC say that Dr. Dyer expects this Bcl-10 discovery to make it easier to develop effective treatment—if scientists can find a way of switching off the mechanism which makes cells malignant.
      This research has generated excitement in the United Kingdom. Earlier work on this gene was dominated by US groups. The scientists and the funders express the hope that Bcl-10 and p53 will together unravel most common cancers. They emphasize that the work is in an early stage.

The research appears in Cell, Vol. 96, 35-45, January 8, 1999 Bcl10 Is Involved in t(1;14)(p22;q32) of MALT B Cell Lymphoma and Mutated in Multiple Tumor Types Tony G. Willis, Martin J. S. Dyer, et al. Department of Haematology and Cytogenetics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom

The study was paid for by the Institute of Cancer Research (UK), the Cancer Research Campaign (UK0, the Leukaemia Research Fund (UK), and the Kay Kendall Leukaemia Fund (UK).

For tape clip by science correspondent James Wilkinson see BBC News report Cancer gene breakthrough Jan 8 1999.

For p53 and other genes under investigation for prostate cancer, you might try searching PubMED at the National Library of Medicine.

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January 8, 1999