Math Analysis: Expansion And Segregation Of Mtdna Mutations During Cell Proliferation

Whereas there is only one nucleus and one nuclear genome, a cell relies on numerous mitochondria - which contain hundreds of copies of the mitochondrial genome (mtDNA) - for its energy supplies. So, when a mutation appears in one copy of the mtDNA within one given cell, it is surrounded by a vast number of normal copies. Surprisingly, when researchers characterized the mtDNA of tumor cells, they found mutations in all copies of mtDNA, in all cells of the tumor, and not in the surrounding healthy tissue. This seems to imply that such mutations are selected for, possibly because they confer an advantage to the cell. Many researchers - but by no means all (the field has enjoyed great controversy) - believe that mutations in mtDNA may contribute to tumorigenesis.

On page 147 (Nature Genetics, Vol. 28, No. 2, 01 June 2001), Hilary Coller (of Fred Hutchinson Cancer Research Center, Seattle, USA) and colleagues present a mathematical analysis of the expansion and segregation of mtDNA mutations during cell proliferation. Their models show that a mutation can end up being carried by all mtDNA copies in a cell owing to successive cell divisions, chance and sheer arithmetic-and without selective advantage. The researchers confirm the predictions of their model with data obtained by analyzing tumors and healthy tissues. As the authors point out, this doesn't rule out that some mtDNA mutations might confer proliferative advantage to tumor cells. Leonard Augenlicht and Barbara Heerdt (of Albert Einstein Cancer Center, New York, USA), in their accompanying News & Views article, review the debate on the relevance of mitochondria to cancer.

CONTACT:

Dr. Hilary Coller
Fred Hutchinson Cancer Research Center
Seattle, Washington, USA.
Telephone: +1 (206) 667 5052
Fax: +1 (206) 667 6877
Email: hcoller@fhcrc.org

Dr. Leonard Augenlicht
Albert Einstein Cancer Center
Bronx, New York, USA.
Telephone: +1 (718) 920-4663
Fax: +1 (718) 882 4464
Email: augen@aecom.yu.edu

(C) Nature Genetics press release.

Message posted by: Trevor M. D'Souza