Mouse genome offers human cancer clue

March 24th, 2011 - 2:31 pm ICT by ANI  

Washington, Mar 24 (ANI): By sequencing the genome of a mouse with cancer, researchers at Washington University School of Medicine in St. Louis have uncovered mutations that also drive cancer in humans.

Senior author Timothy Ley and colleagues sequenced the genomes of nearly 250 cancer patients and their tumours. By comparing the DNA sequences of tumor and healthy cells from each patient, they uncovered a number of novel mutations underlying cancer.

The process, however, is time consuming.

Human tumor cells typically display several hundred mutations and most are background alterations that occur naturally throughout the course of a person’s life.

According to the researchers, the challenge is to sift through the genetic ‘noise’ to find the handful of mutations in each tumor that drive cancer development.

For that, they looked for mutations in mouse models of cancer. These mice are inbred, which suggests they have fewer background mutations.

“This approach gives us a way to rapidly evaluate whether mutations in human tumours are likely to be important,” said Ley.

“If we find mutations that occur in mouse models and we see those same mutations, however rare, in human cancers, they are highly likely to be relevant,” he added.

The current study involved a mouse model for acute promyelocytic leukemia (APL). The disease is a subtype of acute myeloid leukemia, a cancer of the blood and bone marrow.

The investigators inserted into the mouse genome a mutated human gene, called PML-RARA, which is known to initiate APL in patients. Then, they waited a year for full-blown leukemia to develop.

When they sequenced the genome of the mouse tumour cells, they found genetic mutations in three genes, each of which alter a single letter in the DNA sequence and disrupt the instructions for making proteins.

“By establishing that the mutation occurs in other mouse tumour samples and in patients with leukemia, that tells us this mutation is a driver; it almost certainly is relevant for the progression of cancer,” said Ley.

He said the research also highlighted the value of mouse models of cancer to find important mutations in patients.

“There’s been an ongoing debate for 15 years about whether mouse models of cancer are relevant to cancer that develops in people,” he said.

“By sequencing this genome, I think the answer is clear: this mouse model is remarkably similar to the human disease. This gives us a new way to use whole-genome sequencing to rapidly identify the most relevant mutations in human cancers,” he added.

The study is reported online March 23 in the Journal of Clinical Investigation. (ANI)

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