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The Genetics of Pancreatic Cancer

-- The Discoveries

 

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Telomeric and Mitochondrial DNA

Telomeres do what?  Telomeres are the ends of chromosomes.  They are like caps on a fence post, special structures that keep chromosomes from falling apart; when that happens, the chromosome can lose (delete) genes from region, or the broken end can join with other chromosomes to form a translocation. We have found that virtually all of the early forms of pancreatic neoplasia, the precursors to cancer, have dramatically short telomeres.  We believe that this is the underlying reason for many of the genetic changes in pancreatic ducts, changes that over a period of decades can lead to the evolution of a cancer.  Without the loss of so much telomeric DNA, it is possible that people would never get pancreatic cancer.

What do mitochondria have to do with cancer?  The answer to this question may be a surprise.   Mitochondria are the energy powerhouses of the cell, in which oxygen is consumed to produce chemical power for other cell functions.  The mitochondria are not in the cell nucleus where most cellular DNA resides, and mitochondria indeed have their own separate DNA.  The vast majority of pancreatic cancers have mutations in mitochondrial DNA.  But these mutations seldom seem to have an effect on normal mitochondrial functions.  Such mutations may just be a fairly normal accompaniment of aging.  We don't yet know whether mitochondria have any special role in helping to produce cancers.  But because pancreatic cancer cells have such a dramatic increase in the amount of mitochondrial DNA compared to normal cells, it may in the future be easier to detect cancer by detection of the mitochondrial mutations than by detection of mutations in the nuclear DNA.