Remarkable new research overthrows the conventional view that cancer always develops in a steady, stepwise progression. It shows that in some cancers, the genome can be shattered into hundreds of fragments in a single cellular catastrophe, wreaking mutation on a massive scale.
The scars of this chromosomal crisis are seen in cases from across all the common cancer types, accounting for at least one in forty of all cancers. The phenomenon is particularly common in bone cancers, where the distinctively ravaged genome is seen in up to one in four cases.
The team looked at structural changes in the genomes of cancer samples using advanced DNA sequencing technologies. In some cases, they found dramatic structural changes affecting highly localised regions of one or a handful of chromosomes that could not be explained using standard models of DNA damage.
"The results astounded us," says Dr Peter Campbell, from the Cancer Genome Project at the Wellcome Trust Sanger Institute and senior author on the paper. "It seems that in a single cell in a single event, one or more chromosomes basically explode literally into hundreds of fragments.
"In some instances the cancer cases our DNA repair machinery tries to stick the chromosomes back together but gets it disastrously wrong. Out of the hundreds of mutations that result, several promote the development of cancer."
Cancer is typically viewed as a gradual evolution, taking years to accumulate the multiple mutations required to drive the cancer's aggressive growth. Many cancers go through phases of abnormal tissue growth before eventually developing into malignant tumours.
The new results add an important new insight, a new process that must be included in our consideration of cancer genome biology. In some cancers, a chromosomal crisis can generate multiple cancer-causing mutations in a single event.
"We suspect catastrophes such as this might happen occasional
|Contact: Don Powell|
Wellcome Trust Sanger Institute