Article

Lukas Wartman

Doctor survives cancer he studies

Using advanced sequencing and analysis technology, researchers at The Genome Institute and their colleagues have helped their fellow doctor, Lukas Wartman, survive the cancer he studies.

When Lukas Wartman began medical school at Washington University in St. Louis, he knew he wanted to study cancer and treat patients. What he didn't know was that by his fourth year of school, he would end up battling the very disease he was studying.

It was during that last year, in 2003, that Lukas was diagnosed with Acute Lymphoblastic Leukemia, a cancer of the blood that is highly treatable in children, but often fatal in adults.

Short-Lived Victory

After two years of chemotherapy, Lukas’ disease went into remission and he was finally able to finish his clinical training. Unfortunately the victory was short-lived: in 2008, after one year of a clinical oncology fellowship, Lukas relapsed. He was treated again with high-dose chemotherapy and received a stem cell transplant from his younger brother. That put him back in remission and made him more committed than ever to understanding and fighting the terrible disease that had plagued him.

In the laboratory of Dr. Timothy Ley, Lukas has been able to study the genetics underlying leukemias like his own. By sequencing the whole genomes of patients with leukemia, the hope is that they can learn what genetic changes drive the disease and how best to target those changes to stop the cancer.

First Whole Cancer Genome

In 2008, Genome Institute scientists, Dr. Ley and others, published the sequence of the first whole cancer genome – that of a patient with a form of leukemia called Acute Myeloid Leukemia (AML). This marked the beginning of an exciting new way to look at cancer and an advancement that would prove vital to Lukas’ health.

In 2011, Lukas relapsed again. While the chances of an adult surviving one relapse from ALL are slim, there were no statistics about surviving a second relapse. After another round of strong chemotherapy, this time Lukas’ disease did not go into remission. By the end of the summer of 2011, time was running out.

Sequencing His Genome

At the time of his second relapse, Dr. Ley approached Lukas with the suggestion that he join a research study to sequence his whole genome and see if it turned up any new information about his cancer. Lukas was willing to give it a try. DNA samples were prepared and sent to The Genome Institute, which pooled its resources in order to sequence and analyze cancer and normal genomes in a matter of weeks, a process that typically can take months.

By comparing Lukas’ cancer and normal genomes, researchers and analysts at The Genome Institute found a number of changes, or mutations, that were associated with his leukemia. These mutations allowed the research team to determine that there were actually two types of tumor cells present in Lukas’ bone marrow, and further allowed his clinical team to monitor the continued presence of ALL despite the chemotherapy. Unfortunately none of the mutations were treatable with existing drugs. But the team had also generated an additional data set that included an analysis of Lukas’ RNA, a molecule that could give the researchers more information on whether there we any abnormalities in Lukas’ genes.

Additional Data

The task of analyzing the RNA data fell to Genome Institute newcomer, Dr. Malachi Griffith. With a background in molecular biology, biochemistry and computer science, Dr. Griffith performed an integrated analysis of data that included whole genome, exome (the protein-coding genes of the genome) and RNA sequence. When it became clear that no obvious drug targets were revealed by the whole genome sequencing data, Dr. Griffith began to scrutinize the RNA data to see if there were any over or underexpressed genes in the cancer cells. Any such genes would likely play an important role in Lukas’ cancer.

The results of the analysis were encouraging. Dr. Griffith discovered that a gene called FLT3 was being expressed at a much higher level than normal. Using a drug-gene interaction database that he had been developing, Dr. Griffith also found a drug, Sutent, normally used in kidney cancer that targets a “hyperactive” FLT3 gene. Finally they had found something they could act on.

Successful Treatment

With these new results, Lukas’ doctors decided to start him on Sutent to see if it would help him. Amazingly, it put his cancer into remission once again. He has since had another stem cell transplant, and though he has had serious side effects from the transplant, he is doing well.

Without this sequencing data, Lukas’s doctors say he likely would not have survived past the fall of 2011. This integrated approach – sequencing the whole genome, exome and RNA of an individual with cancer – did not exist when Lukas’ leukemia was first diagnosed. But the hope is that this type of analysis will eventually lead to clinical action in the majority of cancer cases. And while this approach to treatment remains expensive, laborious, controversial, and not yet generally available, researchers like Dr. Griffith envision a future where it becomes routine: “We want to be able to take the tumor of every patient that comes into the clinic, sequence their genome and produce a clinical report just like when a physician orders a blood test.”

Watch Lukas' incredible story in this New York Times video: