Acute lymphoblastic leukemia (ALL) is the most common cancer to strike children. One particularly rare form of the disease has been linked to chromosome mutations described as catastrophic and it usually requires more aggressive treatment than other forms of childhood leukemias. A recent study of the genomes of children with the disease found that this particular genetic mutation increases a child's risk of cancer by 2,700 times.

DNA strandResearchers at England's University of Newcastle and Wellcome Trust Sanger Institute used state-of-the-art DNA analysis to reconstruct genetic events backwards, from cancerous to pre-cancerous state, and pinpoint the cellular mechanisms that mark the beginning of disease. The rare but aggressive form of ALL centers on sections of chromosome 21 so the disease is identified accordingly — iAMP21 ALL.

In children with iAMP21 ALL, chromosome 21 on one side of the DNA double helix is fused with another chromosome on the other side of the double helix, often chromosome 15, but some genomes revealed fusion with the opposite chromosome 21. According to co-lead author, University of Newcastle Professor Christine Harrison, "People who carry this specific joining together of chromosomes 15 and 21 are specifically and massively predisposed to iAMP21 ALL."


The catastrophic event occurs when the fused chromosomes shatter in a process called chromothripsis. At that point, normal DNA repair procedures begin but instead of being put back in healthy order, chromosome 21 is reorganized in ways that are so inaccurate it leaves the chromosome highly flawed. The resulting flaws transform the chromosome in ways that promote cancer development.

The genomes of every patient with iAMP21 ALL that the research team sequenced revealed the chromothripsis event followed by erratic reconstruction of chromosome 21. Dr. Peter Campbell, of the Wellcome Trust Sanger Institute, says, "What is striking about our findings is that this type of leukemia could develop incredibly quickly — potentially in just a few rounds of cell division."

Also representing the Wellcome Trust Sanger Institute is Dr. Yilong Li, who describes the disease as "a remarkable cancer." He further states, "For patients with iAMP21 ALL, we see the same part of the genome struck by massive chromosomal rearrangement."

In future research, the team will strive to discover why the mutated chromosomes are so prone to the catastrophic shattering event that triggers cancer development. Also in development is a study using the same DNA sequencing method to track the genetic history of other forms of cancer.


Source: "Leukaemia caused by chromosome catastrophe." Wellcome Trust Sanger Institute / Press. Wellcome Trust Sanger Institute, Genome Research Limited. Mar 23, 2014. Web. Mar 31, 2014.