Genome remodeling may reveal clues to the way tumors spread

Sequencing entire genomes of cancer patients may reveal how tumors spread in breast cancer patients, according to a study published in Nature (2010 Apr 15;464(7291):999-1005).

For their study, researchers led by Li Ding, PhD, research associate professor of genetics, set out to decode the genome of a 44-year-old African-American woman with “triple negative” breast cancer and the genomes of her breast tumor and a metastatic tumor that quickly developed in her brain. Additionally, to determine whether the animal model can reproduce the genetic profile of human cancer, researchers also sequenced the genome of the patient's breast tumor after growing it in a mouse.

When the DNA sequences of the three genomes were compared, researchers identified 20 mutations that occurred at relatively low levels in the patient's breast tumor that were also present at higher levels in metastatic tumor cells.

“This indicates that a small subset of cells with a lethal mutation repertoire break free from the primary tumor, circulate in the body, set up residence in other organs and grow aggressively,” said co-lead author Matthew Ellis, MD, PhD, the Anheuser-Busch Endowed Professor in Medical Oncology. “Mutation enrichment is likely to be important for tumor spread since the mutation enrichment pattern in the brain metastasis and the tumor grown in the mouse strongly overlapped, indicating that the process was not random.”

Researchers also identified a single mutation in the CSMD1 gene, which has been associated with poor survival in invasive ductal breast cancer and is frequently deleted in some colorectal and head and neck cancers.

“We've learned some significant lessons about cancer from sequencing the genomes of individual patients and their tumors, but it's clearly just the tip of the iceberg,” said Richard Wilson, PhD, Director of The Genome Center and a co-author of the new research. “Moving forward, we'll be comparing tumor genomes from many patients with the same type of cancer to find common genetic alterations. This comprehensive understanding of cancer can aid in the development of new approaches to cancer diagnosis and treatment.”

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