Scientists sequence genome of second patient with AML

In collaboration with the Press Association

US scientists have decoded the complete DNA sequence - or 'genome' - of a second patient with acute myeloid leukaemia (AML), following on from the first such achievement last year.

The advance has revealed a number of genetic changes in the patient's cancer cells, including one 'fault' that is also known to be involved in a form of brain tumour called a glioma, and another 'fault' - not previously linked to AML - that has now been found in two patients with this type of leukaemia.

Scientists at the Washington University School of Medicine in St Louis believe that their findings show that sequencing cancer genomes could have enormous potential in developing new treatments.


Senior author Dr Timothy Ley, haematologist and professor of medicine, commented: "Only by sequencing complete genomes of cancer patients are we going to find unexpected, recurring genetic mutations that are highly likely to be important for cancer to develop and grow.

"Gaining a genome-wide understanding of cancer lays the foundation for developing more powerful ways to diagnose, classify and treat patients."

In the latest study, researchers sequenced the genome of a man who was diagnosed with AML at 38 years of age who has been in remission for more than three years.

They used a sample of his healthy skin cells to sequence his genome, as well as a sample of tumour cells taken from his bone marrow.

This allowed them to look for genetic alterations that were present in tumour cells but not in his healthy cells.

Dr Ley explained that little is known about how and why different people respond to different treatments, so most people with AML are given similar cancer therapy.

"By defining the mutations that cause AML in different people, we hope to determine which patients need aggressive treatment, like a stem cell transplant, and which can be treated effectively with less intense therapies," he revealed.

The researchers identified around 750 mutations in the patient's tumour genome, including 64 that were thought to be related to his AML. The others are believed to be random, background mutations that were not related to the disease.

Twelve of the 64 mutations were found in genes that instruct cells how to make specific proteins, while the remainder were in the stretches of DNA between genes. Previously known as 'junk' DNA, these regions are now thought to influence the way in which genes work and are not yet properly understood.

Co-author Dr Richard Wilson, director of Washington University's Genome Centre, said the discovery of so many new mutations came as a "huge" surprise.

"That so many of the mutations were found outside of protein-coding genes also underscores the need to sequence whole genomes to find all the mutations that occur in cancer," he observed.

"If we only look at genes with known or suspected links to cancer, we'll miss many mutations that are potentially relevant."

The researchers then tested 187 DNA samples from other AML patients and discovered that one of the 64 mutations, which affects a gene called IDH1, was present in 15 of the samples, indicating that it is likely to be important in the disease's progress.

Dr Jodie Moffat, Cancer Research UK's senior health information officer, said: "It's exciting that these detailed studies to understand the genetic basis of cancer are now possible due to advances in technology.

"The genetic factors involved in leukaemia are particularly complex, so anything new we can learn is very welcome. But further research will be needed before scientists can reveal which parts of the genetic puzzle can actually be used to improve the lives of cancer patients."

The team is now sequencing more DNA samples from AML patients, as well as samples from people with breast, lung and ovarian cancers and glioblastomas.


 Mardis, E. et al (2009). Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome New England Journal of Medicine DOI: 10.1056/NEJMoa0903840