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Washington University scientists first to sequence genome of cancer patient

changes that altered the instructions for making proteins.

Of the eight novel mutations discovered, three were found in genes that normally act to suppress tumor growth. One of these mutations is in the PTPRT tyrosine phosphatase gene, which is frequently altered in colon cancer.

Four other mutated genes appear to be involved in molecular pathways that promote cancer growth. In particular, one mutation was found in a gene family that also is expressed in embryonic stem cells and may be involved with cell self-renewal. Interestingly, the researchers note, self-renewal is thought to be an essential feature of leukemia cells.

Another gene alteration appears to affect the transport of drugs into the cell, and may have contributed to the patient's chemotherapy resistance.

"We're still analyzing the patient's non-coding DNA and expect to find a number of additional relevant mutations in this portion of the genome," says Elaine Mardis, Ph.D., co-lead author of the study and co-director of the Genome Sequencing Center. "But the role of these non-coding mutations will be more of a challenge to elucidate because we do not yet fully understand the function of this part of the genome."

The team also looked to see if the eight novel mutations in the patient's tumor genome also occurred in the DNA of tumor samples from 187 additional AML patients. None of those tumors had any of the eight mutations.

"This suggests that there is a tremendous amount of genetic diversity in cancer, even in this one disease," Wilson says. "There are probably many, many ways to mutate a small number of genes to get the same result, and we're only looking at the tip of the iceberg in terms of identifying the combinations of genetic mutations that can lead to AML."

Based on their current understanding of cancer, the researchers suspect that the mutations occurred sequentially. The first mutation gave the cell a slight tendency toward cancer

Contact: Caroline Arbanas
Washington University School of Medicine

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