Title: "DNA methylation patterns tell a tale of cancer stem cells"
Speaker: Kim Siegmund, Department of Preventive Medicine, University of Southern California
Place: MATH 175; November 15, 2007, THURSDAY, 4:30pm (NOTE: date and location change)

Abstract

Cancer is believed to start from a single transformed cell and progress through a series of clonal expansions. However, virtually nothing is known about the phylogenetic structure of individual human cancers. Cancer cells are thought to be immortal, in the sense that given the right conditions, unlimited progeny are possible. However, recent studies have suggested a hierarchy of cancer cells consisting of relatively rare cancer "stem" cells that produce much larger numbers of "differentiated" cancer cells which have more limited proliferative potential. Cancer growth requires genome replication that, just like phylogeny, can be summarized using ancestral trees. Genome replication involves both the duplication of base order and the duplication of epigenetic patterns such as DNA methylation at CpG sites. At certain genomic sequences, DNA methylation errors accumulate at much faster rates than mutations. We explore a population genetic approach to reconstruct tumor histories from non-functional replication errors, using DNA methylation as a somatic cell "molecular clock". We apply rejection methods to analyze data from three human cancers, finding evidence supporting the existence of cancer stem cells. We also estimate age of the tumor, a variable of considerable interest to epidemiologists who are trying to identify different disease pathways by identifying "young" tumors that may be extremely aggressive from "old" tumors that may be relatively benign.

Related Reading:
Paul Marjoram and Simon Tavare. 2006. Modern computational approaches for analysing molecular genetic variation data. Nature Reviews Genetics. 7:759-770.



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