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Mouse cancer genome unveils genetic errors in human cancers
Date:3/23/2011

Scientists who pioneered sequencing the genomes of cancer patients to find novel genetic changes at the root of the disease now have turned their attention to a laboratory workhorse a mouse.

By sequencing the genome of a mouse with cancer, researchers at Washington University School of Medicine in St. Louis have uncovered mutations that also drive cancer in humans. The investigators are the first to sequence a mouse cancer genome, and their research is reported online March 23 in the Journal of Clinical Investigation.

"This approach gives us a way to rapidly evaluate whether mutations in human tumors are likely to be important," says senior author Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology. "If we find mutations that occur in mouse models and we see those same mutations, however rare, in human cancers, they are highly likely to be relevant."

Ley and his colleagues at Washington University's Genome Institute have sequenced the genomes of nearly 250 cancer patients and their tumors. By comparing the DNA sequences of tumor and healthy cells from each patient, they have uncovered a number of novel mutations underlying cancer.

But the endeavor is time consuming. Human tumor cells typically acquire several hundred mutations; the vast majority are background alterations that occur naturally throughout the course of a person's life. The challenge is to sift through the genetic "noise" to find the handful of mutations in each tumor that drive cancer development.

Ley and his colleagues theorized that their work could be simplified if they looked for mutations in mouse models of cancer. These mice are inbred, which suggests they have fewer background mutations.

The current study involved a mouse model for acute promyelocytic leukemia (APL) that was developed in Ley's lab more than a decade ago by Peter Westervelt, MD, PhD, now director of the Bone Marrow Transplant/Leukemia Sectio
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert

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