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Genome Sequencing Breast Tumor Progression

With the help of DNA sequencing technology, scientists at Washington University School of Medicine in St. Louis are getting an unprecedented look at the genetic basis of a highly lethal breast cancer that disproportionately affects younger women and those who are African-American.

Washington University scientists have decoded the entire genome of a 44-year-old African-American woman with so-called “triple-negative” breast cancer, along with the genomes of her breast tumor and a metastatic tumor that quickly developed in her brain. By comparing the DNA sequences of the three genomes, the scientists have identified 20 genetic changes from a subset of cells in the woman’s breast tumor that likely played a role in the metastasis that killed her within months. The research appeared in the journal Nature.

“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,” says co-lead author Matthew Ellis, MD, PhD, the Anheuser-Busch Endowed Chair in Medical Oncology and a breast cancer specialist with the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The patient, the first African-American to have her genome sequenced, had an aggressive “basal-like” subtype of breast cancer. These genetically unstable tumors account for about 10 percent of all breast cancers and often are called triple-negative because they lack any receptors to which treatment can be targeted. They grow rapidly and often do not respond to chemotherapy.

The researchers now are decoding the genomes of additional women with basal-like breast cancer to determine whether mutations in their primary tumors also influence the spread of the disease.

“We are getting an intimate look at the lethal spread of a breast cancer,” says senior author Elaine Mardis, PhD, co-director of Washington University’s Genome Center. “This work lays the foundation for understanding the genetic basis of tumor progression and metastasis and for identifying new drug targets that can improve the outlook for women with this disease.”
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