DOI: 10.1097/01.COT.0000372161.61560.9b
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Issn Print: 0276-2234
Publication Date: 2010/04/25
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Excerpt
Because epigenetic changes occur at relatively high frequency, in contrast to DNA mutations, the hope, researchers say, is that epigenetic research can help better define disease characteristics, determine prognosis, and measure drug efficacy in clinical trials. Epigenetic changes can also be pharmacologically modified without changing genetic sequence.
In cancer, measuring gene expression and detecting genetic mutations is not enough, said Ari M. Melnick, MD, Director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences as well as the Epigenomics Core Facility at Weill Cornell Medical College in New York City, lead author of one of the studies (Figueroa ME et al: Cancer Cell 2010;17:13–27). “Cancer is an epigenetic disease, not only a genetic disorder.”
Epigenetic marks including DNA methylation, histone modifications, and microRNAs control the timing, levels, and even the splicing of genes. Applications of genetic research in cancer have been limited until now, but the three studies represent progress in moving basic epigenetics research to the clinic.
The first author of the second study (Blood 2010;115:636-6), Lars Bullinger, MD, a hematology-oncology fellow at the University of Ulm in Germany, explained that in AML, as in other cancers, DNA methylation plays a critical role, with implications for diagnosis and treatment. Epigenetic research in leukemia is a bit ahead of work in most solid tumors except for colorectal cancer, in part because of the ease of obtaining cells in blood vs obtaining tumor samples, which also have greater heterogeneity.
“Leukemias are characterized by fusion proteins and genetic translocations, many of which also have epigenetic causes,” said Manel Esteller, MD, PhD, Director of the Center for Cancer Epigenomics and Biology Program at the University of Barcelona, coauthor of the third study, a poster presented by Sara Alvarez, MD, PhD, at the most recent American Society of Hematology Annual Meeting (Abstract 2394).
Taken together, the new data show that understanding epigenetic changes in AML can give clinicians a clearer, more complete picture of how the disease develops, can help determine which patients have more resistant or less resistant disease, and can point to better ways of treating both types of patients and gauge the efficacy of treatments.
