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Investigating a new PPM1D mutation in lymphoma, breast, and bowel cancer

  • Researcher: Dr Libor Macurek
  • Institution: Institute of Molecular Genetics, Prague, Czech Republic
  • Award Amount: £129,492 for 3 years from June 2014
  • Cancer Type: Bowel Cancer
Investigating a new PPM1D mutation in lymphoma, breast, and bowel cancer
The PPM1D gene recently hit the news when scientists reported mutations in the gene may be linked to an increased risk of breast and ovarian cancer. But what is not known is exactly why PPM1D mutations could be so dangerous for some people.Dr Macurek and his team in Prague, Czech Republic have independently identified a different mutation in PPM1D and have gathered evidence suggesting why they think this mutation may cause cells to become cancerous. In this new project they will use a whole range of techniques to see if they are right. The mutation Dr Macurek has identified causes PPM1D to produce a protein which is much shorter than usual. This protein is part of the cell ‘checkpoint’ machinery, which works to protect cells from becoming cancerous. It does this by making sure cells with damaged DNA are prevented from growing and dividing until the DNA has been repaired. The PPM1D protein’s role is to switch off the checkpoint machinery so the cell can continue growing. But Dr Macurek thinks that the short version of the protein is almost too good at its job, shutting down the checkpoint machinery too soon and before DNA damage has been repaired. This could spell disaster and allow cells to divide without any control. Using human cells grown in the lab, Dr Macurek will study how this shortened protein may affect the checkpoint process and if these cells respond differently to chemotherapy. He will also investigate in mice if and how this shortened protein affects development of lymphoma, breast cancer, and bowel cancer. Finally the team will screening patient samples for PPM1D mutations, to establish if these mutations may also be linked to increased risk of bowel cancer.
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